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The role of brain dopamine systems in anticipatory and consummatory aspects of sexual behavior in the… Pfaus, James George 1990

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THE  ROLE OF BRAIN DOPAMINE SYSTEMS IN ANTICIPATORY AND  CONSUMMATORY ASPECTS OF SEXUAL BEHAVIOR IN THE MALE RAT by JAMES GEORGE PFAUS  B.A., The American U n i v e r s i t y , 1983 M.A., U n i v e r s i t y o f B r i t i s h Columbia, 1986  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE  FACULTY OF GRADUATE STUDIES Department o f Psychology  We a c c e p t t h i s  t h e s i s as conforming  to the r e q u i r e d  THE  standard  UNIVERSITY OF BRITISH COLUMBIA A p r i l 1990 ©  James George Pfaus, 1990  In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department  or by his  or her  representatives.  It  is  understood  that  copying or  publication of this thesis for financial gain shall not be allowed without my written permission.  Department of The University of British Columbia Vancouver, Canada Date  DE-6 (2/88)  Abstract The r o l e of b r a i n dopamine  (DA) systems i n the c o n t r o l of  a n t i c i p a t o r y and consummatory a s p e c t s of the s e x u a l behavior of male r a t s was examined i n the p r e s e n t experiments. e x p l o r e d the s t a t i s t i c a l  Experiment I  r e l a t i o n s h i p among a n t i c i p a t o r y and  consummatory measures of male s e x u a l behavior u s i n g correlations  and f a c t o r a n a l y s i s .  anticipatory behavioral  Level  changing, a measure of  excitement, was not r e l a t e d  to any of the consummatory measures of c o p u l a t i o n , several  consummatory measures were c o r r e l a t e d .  analysis  revealed  initiation, tentative  statistically whereas  The f a c t o r  the e x i s t e n c e of f i v e f a c t o r s : c o p u l a t o r y  h i t r a t e , mount count, and a n t i c i p a t i o n ;  names.based on the measures t h a t  onto each f a c t o r . and  multiple  given  loaded most  These r e s u l t s e s t a b l i s h e d  that  rate,  heavily  anticipatory  consummatory measures of* male s e x u a l b e h a v i o r a r e  unrelated  statistically. Experiment I I examined the dose-response e f f e c t s of s e v e r a l DA r e c e p t o r a n t a g o n i s t s on a n t i c i p a t o r y of male s e x u a l b e h a v i o r . neuroleptics  haloperidol  and consummatory measures  Systemic a d m i n i s t r a t i o n  of the t y p i c a l  and pimozide, and the D l - s e l e c t i v e  a n t a g o n i s t SCH 23390, s i g n i f i c a n t l y reduced the number of l e v e l changes, i n c r e a s e d  the i n t r o m i s s i o n  number of i n t r o m i s s i o n s The a t y p i c a l n e u r o l e p t i c  l a t e n c i e s , and decreased the  and the t o t a l number of clozapine  and the  ejaculations.  D2-selective  a n t a g o n i s t s u l p i r i d e reduced the number of l e v e l changes and significantly  increased  the i n t r o m i s s i o n  l a t e n c i e s , but d i d not  a f f e c t the number of i n t r o m i s s i o n s every case, the doses r e q u i r e d lower than those r e q u i r e d  or e j a c u l a t i o n s .  t o reduce l e v e l changing were  to increase  the i n t r o m i s s i o n l a t e n c i e s ,  i n d i c a t i n g t h a t the measure of a n t i c i p a t o r y s e x u a l more s e n s i t i v e t o d i s r u p t i o n by DA a n t a g o n i s t s consummatory measures of s e x u a l  In almost  behavior.  behavior  than were  The a n t i e m e t i c  metoclopramide decreased the number of i n t r o m i s s i o n s a f f e c t other  was  agent  but d i d not  a n t i c i p a t o r y or consummatory measures of s e x u a l  behavior s i g n i f i c a n t l y .  High doses of h a l o p e r i d o l , pimozide, or  c l o z a p i n e d e l a y e d or a b o l i s h e d of c o p u l a t i o n .  l e v e l changing and the i n i t i a t i o n  These r e s u l t s i n d i c a t e d t h a t a n t i c i p a t o r y and  consummatory measures of male s e x u a l d i f f e r e n t i a l l y by DA  behavior a r e a f f e c t e d  antagonists.  Experiment I I I p r o v i d e d  the f i r s t  evidence t h a t  haloperidol  a f f e c t s a n t i c i p a t o r y and consummatory measures of male  sexual  b e h a v i o r s e l e c t i v e l y i n d i f f e r e n t b r a i n DA t e r m i n a l s .  Bilateral  i n f u s i o n s of h a l o p e r i d o l t o the nucleus accumbens reduced changing without a f f e c t i n g the i n i t i a t i o n consummatory measures. striatum  increased  a f f e c t other  Bilateral  of c o p u l a t i o n  level  or other  i n f u s i o n s of h a l o p e r i d o l t o the  the t o t a l number of e j a c u l a t i o n s but d i d not  consummatory or a n t i c i p a t o r y measures.  i n f u s i o n s of h a l o p e r i d o l t o the medial p r e o p t i c area produced n e a r l y a l l of the e f f e c t s of s y s t e m i c  Unilateral (MPOA)  administration,  i n c l u d i n g reduced number of l e v e l changes, i n c r e a s e d  intromission  l a t e n c i e s , and decreased number of i n t r o m i s s i o n s and ejaculations.  These r e s u l t s i n d i c a t e d t h a t DA i n the nucleus  accumbens and s t r i a t u m are a n t i c i p a t o r y sexual  involved  behavior  and c o p u l a t o r y  whereas DA i n t h e MPOA i s i n v o l v e d behavior,  the i n i t i a t i o n  i n the d i s p l a y of rate, respectively,  i n a n t i c i p a t o r y sexual  of c o p u l a t i o n , and c o p u l a t o r y  rate.  In Experiment IV, i n v i v o voltammetry r e v e a l e d a differential  p a t t e r n of DA e f f l u x  i n t h e nucleus accumbens and  s t r i a t u m , and catecholamine e f f l u x i n t h e MPOA, d u r i n g a n t i c i p a t o r y and consummatory phases o f s e x u a l rats.  Increased  DA e f f l u x  catecholamine e f f l u x presentation initiation  behavior  i n male  i n t h e n u c l e u s accumbens and i n c r e a s e d  i n t h e MPOA were a s s o c i a t e d with t h e  of a r e c e p t i v e female behind a s c r e e n  of c o p u l a t i o n .  E f f l u x i n both r e g i o n s  and with t h e decreased  f o l l o w i n g e j a c u l a t i o n but i n c r e a s e d p r i o r t o each r e i n i t i a t i o n of copulation. during general  DA e f f l u x  copulation.  i n the s t r i a t u m increased n o n s p e c i f i c a l l y  Use o f i n v i v o m i c r o d i a l y s i s confirmed t h e  p a t t e r n of DA e f f l u x  s t r i a t u m observed with  i n t h e n u c l e u s accumbens and  voltammetry.  These r e s u l t s were i n t e r p r e t e d as s u p p o r t i n g  a r o l e of DA  terminals  i n t h e nucleus accumbens and MPOA, but not t h e  striatum,  i n t h e d i s p l a y of a n t i c i p a t o r y s e x u a l  the  initiation  of c o p u l a t i o n .  behavior  In p a r t i c u l a r , t h e i n c r e a s e d  r e l e a s e of DA i n t h e MPOA was viewed as s e n s i t i z i n g mechanisms i n v o l v e d increased  and i n  hypothalamic  i n the c o n t r o l of p e n i l e e r e c t i o n whereas t h e  r e l e a s e of DA i n t h e nucleus accumbens was viewed as  s e n s i t i z i n g motor programs n e c e s s a r y f o r t h e e x e c u t i o n of a n t i c i p a t o r y sexual  responses and t h e i n i t i a t i o n  of mounting.  V  T a b l e of Contents Abstract  ...  List  of T a b l e s  List  of F i g u r e s  .  i i viii ix  Acknowledgements  xi  INTRODUCTION  1  The n e u r o b i o l o g y of dopamine Dopamine and i n c e n t i v e m o t i v a t i o n Relevance  1 ............. — . . .  of dopamine t o s e x u a l behavior  9  D e s c r i p t i o n of the s e x u a l behavior of male r a t s Role of dopamine i n the s e x u a l behavior  . .  45  Overview of the present experiments  48  STATISTICAL ANALYSIS OF MALE SEXUAL BEHAVIOR IN THE BI LEVEL CHAMBER  Method  51  .  57  R e s u l t s and D i s c u s s i o n  EXPERIMENT I I :  60  EFFECTS OF SYSTEMIC ADMINISTRATION OF DOPAMINE ANTAGONISTS ON ANTICIPATORY AND  CONSUMMATORY  ASPECTS OF SEXUAL BEHAVIOR IN THE MALE RAT. Method  22  A new measure of a n t i c i p a t o r y s e x u a l  behavior  EXPERIMENT I :  13  of male r a t s :  A review L e v e l changing:  6  76 78  vi Results  81  Discussion  . ...  EXPERIMENT I I I :  106  EFFECTS OF CENTRAL ADMINISTRATION OF HALOPERIDOL ON ANTICIPATORY AND CONSUMMATORY ASPECTS OF SEXUAL BEHAVIOR I N THE MALE RAT  114  Method  117  Results  124  Discussion  133  EXPERIMENT I V :  ELECTROCHEMICAL DETECTION OF CENTRAL DOPAMINE EFFLUX DURING ANTICIPATORY AND CONSUMMATORY  Experiment  PHASES OF SEXUAL BEHAVIOR I N THE MALE RAT . .  140  IVa:  14 6  Method  146  Results  153  Discussion  162  Experiment  IVb:  165  Method  166  Results  168  Discussion  172  Experiment  IVc:  175  Method Results Discussion  177 .  183 192  vii GENERAL DISCUSSION The r o l e  of  198  b r a i n dopamine systems  i n male  sexual  behavior Clinical  205  implications  Male s e x u a l  behavior  219 as a f o r m o f m o t i v a t e d  Summary and c o n c l u s i o n s  REFERENCES  behavior  ..  223 226  228  viii List  of  Tables  Table  I.  Means, s t a n d a r d e r r o r s , and i n t e r c o r r e l a t i o n s among t h e 11 m e a s u r e s o f s e x u a l b e h a v i o r d i s p l a y e d b y male r a t s i n t h e b i l e v e l chambers 61  Table  II.  Correlation coefficients s i g n i f i c a n c e o f p_<.05  Table Table  I I I . Estimates of communality sexual behavior IV.  Factors  and t h e i r  with  statistical 62  for  variable  each measure  of 66  loadings  67  ix List Figure  Figure  of  Figures  1 . Schematic r e p r e s e n t a t i o n of the major g r o u p s and t h e i r e f f e r e n t * p r o j e c t i o n s brain  DA c e l l in the r a t  2. L e v e l changes d i s p l a y e d by s e x u a l l y a c t i v e i n t h e b i l e v e l chambers  4  males 47  Figure  3.  Percentage of r a t s d i s p l a y i n g l e v e l changes, mounts, i n t r o m i s s i o n s , and e j a c u l a t i o n s f o l l o w i n g t r e a t m e n t w i t h h a l o p e r i d o l i n Experiment I I 83  Figure  4 . E f f e c t o f h a l o p e r i d o l on t h e 9 p r i m a r y m e a s u r e s male s e x u a l b e h a v i o r i n E x p e r i m e n t I I  of 85  Figure  5. P e r c e n t a g e of r a t s d i s p l a y i n g l e v e l changes, mounts, i n t r o m i s s i o n s , and e j a c u l a t i o n s f o l l o w i n g t r e a t m e n t w i t h p i m o z i d e in Experiment I I 88  Figure  6. E f f e c t o f p i m o z i d e on t h e 9 p r i m a r y m e a s u r e s male s e x u a l b e h a v i o r i n E x p e r i m e n t I I  Figure  7.  Figure  8 . E f f e c t o f c l o z a p i n e on t h e 9 p r i m a r y m e a s u r e s male s e x u a l b e h a v i o r i n E x p e r i m e n t I I  Figure  of 90  Percentage of r a t s d i s p l a y i n g l e v e l changes, mounts, i n t r o m i s s i o n s , and e j a c u l a t i o n s f o l l o w i n g t r e a t m e n t w i t h clozapine i n Experiment I I . . 93  9 . E f f e c t o f m e t o c l o p r a m i d e on t h e 9 p r i m a r y o f male s e x u a l b e h a v i o r i n E x p e r i m e n t I I  of 95  measures 98  Figure  10. Percentage of r a t s d i s p l a y i n g l e v e l changes, mounts, i n t r o m i s s i o n s , and e j a c u l a t i o n s f o l l o w i n g t r e a t m e n t w i t h SCH 23390 i n E x p e r i m e n t I I 101  Figure  1 1 . E f f e c t o f SCH 23390 on t h e 9 p r i m a r y m e a s u r e s male s e x u a l b e h a v i o r i n E x p e r i m e n t I I  of  1 2 . E f f e c t o f s u l p i r i d e on t h e 9 p r i m a r y m e a s u r e s male s e x u a l b e h a v i o r i n E x p e r i m e n t I I  of  Figure Figure Figure Figure  13. B i l a t e r a l cannula placements d i r e c t e d n u c l e u s accumbens i n E x p e r i m e n t I I I  at  14. B i l a t e r a l cannula placements d i r e c t e d s t r i a t u m i n Experiment I I I  at  15. U n i l a t e r a l cannula placements d i r e c t e d medial p r e o p t i c area in Experiment i l l  103 105  the 121 the 122  at  the 123  X  Figure  Figure  Figure  Figure Figure Figure Figure  Figure  Figure  16. E f f e c t of b i l a t e r a l i n f u s i o n s of h a l o p e r i d o l t o t h e n u c l e u s accumbens on m e a s u r e s o f male s e x u a l behavior i n Experiment I I I  126  17. E f f e c t of b i l a t e r a l i n f u s i o n s of h a l o p e r i d o l t o t h e s t r i a t u m on m e a s u r e s o f male s e x u a l b e h a v i o r i n Experiment I I I  129  18. E f f e c t of u n i l a t e r a l i n f u s i o n s of h a l o p e r i d o l t h e m e d i a l p r e o p t i c a r e a on m e a s u r e s o f m a l e sexual behavior in Experiment I I I  131  19. E l e c t r o d e placements d i r e c t e d accumbens i n E x p e r i m e n t I V a  at  20. E l e c t r o d e placements d i r e c t e d Experiment IVa  at  the  to  nucleus 149  2 1 . E l e c t r o d e placements d i r e c t e d at p r e o p t i c area i n Experiment IVa  the s t r i a t u m  in 150  the  medial  2 2 . Changes i n DA o x i d a t i o n c u r r e n t i n t h e accumbens d u r i n g p h a s e s o f male s e x u a l i n Experiment IVa  151 nucleus behavior  155  2 3 . Changes i n DA o x i d a t i o n c u r r e n t i n t h e s t r i a t u m d u r i n g phases o f male s e x u a l b e h a v i o r i n Experiment IVa  158  2 4 . Changes i n c a t e c h o l a m i n e o x i d a t i o n c u r r e n t i n m e d i a l p r e o p t i c a r e a d u r i n g p h a s e s o f male sexual behavior i n Experiment IVa  161  the  Figure  2 5 . Changes i n DA o x i d a t i o n c u r r e n t i n t h e n u c l e u s accumbens and s t r i a t u m , and c h a n g e s i n c a t e c h o l a m i n e o x i d a t i o n c u r r e n t in the medial p r e o p t i c area, d u r i n g the p r e s e n t a t i o n of v a r i o u s s t i m u l i behind t h e s c r e e n , i n E x p e r i m e n t IVb 171  Figure  26. M i c r o d i a l y s i s probe placements d i r e c t e d n u c l e u s accumbens i n E x p e r i m e n t I V c  at  27. M i c r o d i a l y s i s probe placements d i r e c t e d s t r i a t u m i n Experiment IVc  at  Figure  the 181 the 182  Figure  2 8 . L e v e l s o f DA and i t s m e t a b o l i t e s i n d i a l y s a t e s f r o m t h e n u c l e u s accumbens d u r i n g p h a s e s o f male s e x u a l behavior i n Experiment IVc 187  Figure  2 9 . L e v e l s o f DA and i t s m e t a b o l i t e s i n d i a l y s a t e s f r o m t h e s t r i a t u m d u r i n g phases of male s e x u a l b e h a v i o r i n Experiment IVc 191  Acknowledgements I am indebted to my a d v i s o r , Tony P h i l l i p s , f o r h i s encouragement, p a t i e n c e , and support throughout the course of my r e s e a r c h i n h i s l a b o r a t o r y and d u r i n g the p r e p a r a t i o n of t h i s thesis. Our many d i s c u s s i o n s about the r o l e of dopamine i n motivated behavior kept me on t r a c k and helped frame the ideas put forward here. I am a l s o indebted to John P i n e l f o r being a f r i e n d and t e a c h e r , and f o r p r o v i d i n g me with l a b o r a t o r y space f o r s e v e r a l of the experiments r e p o r t e d i n t h i s t h e s i s . The c o n f i d e n c e t h a t both Tony and John showed i n my a b i l i t i e s kept me i n graduate s c h o o l at a time when my own c o n f i d e n c e was waning. I would l i k e to thank the other member of my t h e s i s committee, D i m i t r i Papageorgis, f o r h e l p i n g to make t h i s whole endeavor i n t e r e s t i n g and r e l e v a n t . I would a l s o l i k e to thank S c o t t Mendelson, Jim Blackburn, Mike Mana, Jon Druhan, Joe K l a n c n i k , Tim Harpur, Chuck Blaha, Cathy Rankin, Dave Mumby, Emma Wood, L o r i n d a Holmes, and B a r r y E v e r i t t f o r many hours of d i s c u s s i o n and d i g r e s s i o n . The t e c h n i c a l a s s i s t a n c e of Chuck Blaha, Mike Jung, Shayne K a r d e l , and Fred LePiane i s a p p r e c i a t e d . I am a l s o g r a t e f u l to Geert Damsma, George Nomikos, D a n i e l l e Wenkstern, and C h r i s F i b i g e r at the D i v i s i o n of N e u r o l o g i c a l S c i e n c e s , Department of P s y c h i a t r y , f o r a l l o w i n g me to use t h e i r f a c i l i t i e s and e x p e r t i s e to perform the m i c r o d i a l y s i s experiments. What began t h e r e as j u s t another q u e s t i o n r e s u l t e d i n a h i g h l y s u c c e s s f u l and c r e a t i v e c o l l a b o r a t i o n . F i n a l l y , I would l i k e to thank K r i s t i n Buhrmann. She knows why. T h i s t h e s i s i s d e d i c a t e d to the l a t e Frank Ambrose Beach (1911-1988), whose p i o n e e r i n g e f f o r t s and p e n e t r a t i n g i n s i g h t s i n t o the n e u r o b i o l o g y of mammalian s e x u a l behavior remain a source of g r e a t i n s p i r a t i o n .  1 THE  ROLE OF BRAIN DOPAMINE SYSTEMS IN ANTICIPATORY AND  CONSUMMATORY ASPECTS OF SEXUAL BEHAVIOR IN THE MALE RAT  T h i s t h e s i s has two o b j e c t i v e s .  The f i r s t  i s to describe  the r o l e of b r a i n dopamine (DA) systems i n v a r i o u s a s p e c t s s e x u a l m o t i v a t i o n and c o p u l a t o r y behavior  of male r a t s .  The  second i s t o r e l a t e the r o l e of DA i n male s e x u a l behavior more g e n e r a l r o l e t h a t DA p l a y s motivation.  Although  independently, the of  these  two l i n e s of r e s e a r c h have advanced  i n t r o d u c t i o n of t h i s t h e s i s f i r s t  reviewing  Accordingly,  o u t l i n e s the n e u r o b i o l o g y  i n incentive motivation  the human and animal  before  l i t e r a t u r e on the r o l e of DA i n  male s e x u a l b e h a v i o r .  T h i s review  several methodological  and t h e o r e t i c a l c r i t i c i s m s , most  of the l i t e r a t u r e  leads t o  t h a t knowledge of the r o l e of DA i n the s e x u a l behavior r a t s has not kept of  DA i n motivated  motivation  t o the  i n the r e g u l a t i o n of i n c e n t i v e  t h e i r convergence i s long overdue.  DA and i t s proposed r o l e  of the  notably, of male  pace with more g e n e r a l t h e o r i e s about the r o l e behaviors.  A new method of a s s e s s i n g  i n male r a t s i s presented  as p a r t of an i n t e g r a t e d  approach t o the study of DA i n male s e x u a l behavior behavioral, pharmacological,  The  and e l e c t r o c h e m i c a l  Neurobiology  sexual  t h a t combines  techniques.  of Dopamine  Dopamine was o r i g i n a l l y proposed as a n e u r o t r a n s m i t t e r i n the l a t e 1950s ( B e r t l e r & Rosengren, 1959; C a r l s s o n , 1959; C a r l s s o n , L i n d q v i s t , Magnusson, & Waldeck, 1958; Montague, 1957).  2 Subsequent h i s t o f l u o r e s c e n c e techniques c o n c e n t r a t i o n s of DA thus s a t i s f y i n g classification. DA was  provided  an  in specific  important  microscopy t h a t DA was synaptic terminals. localization fibres,  and  Fuxe, 1964;  these  identification  s e v e r a l DA a g o n i s t s  bromocriptine) disease.  and  techniques, cell  the  neuroanatomic  bodies, p r o j e c t i o n "  described  in d e t a i l  (Dahlstrom  i s shown i n F i g u r e  1.  the DA p r e c u r s o r  (e.g., apomorphine', p i r i b i d e l , the symptoms of  f l u p e n t h i x o l ) , butyrophenones  and  Parkinson's  thioxanthenes  s u c c e s s f u l t h e r a p e u t i c value (Wyatt, 1976).  had  i n the treatment  emerged  the with  of v a r i o u s  In a d d i t i o n , a n t i p s y c h o t i c or  n e u r o l e p t i c drugs were subsequently  shown to antagonize  b e h a v i o r a l e f f e c t s ' o f DA a g o n i s t s and  p r e c u r s o r s , to  the  antagonize  the s i n g l e - u n i t e f f e c t s of i o n t o p h o r e t i c a l l y - a p p l i e d DA, DA-stimulated of  adenylate  the  (e.g., c i s -  (e.g., h a l o p e r i d o l ) , and  s u b s t i t u t e d benzamides (e.g., s u l p i r i d e ) ,  was  1-DOPA  four c l a s s e s of p u t a t i v e DA a n t a g o n i s t s ,  (e.g., c h l o r p r o m a z i n e ) ,  &  1977;  of DA as a major s y n a p t i c t r a n s m i t t e r  could attenuate  Likewise,  phenothiazines  psychoses  role for  demonstrated with e l e c t r o n  complemented by demonstrations t h a t both and  neurotransmitter  H o k f e l t , Johannson, Fuxe, G o l d s t e i n , & Park,  Jacobowitz & P a l k o v i t s , 1972) The  ( C a r l s s o n , 1963),  i n dense core v e s i c l e s w i t h i n  of major DA-containing t e r m i n a l r e g i o n s was  intracellular  of a n e u r o t r a n s m i t t e r  (1968) who  contained  Using  b r a i n areas  c r i t e r i o n of  F u r t h e r evidence by H o k f e l t  revealed  c y c l a s e , and  to block  to i n c r e a s e the f i r i n g  DA neurons by compensatory t r a n s n e u r o n a l  feedback.  rate  3  Figure  1.  S c h e m a t i c r e p r e s e n t a t i o n o f t h e m a j o r DA c e l l g r o u p s and t h e i r e f f e r e n t p r o j e c t i o n s i n t h e r a t b r a i n . A: M e s o t e l e n c e p h a l i c and r e t i n a l DA s y s t e m s ( A 8 , A 9 , A 1 0 , A 1 6 , and A 1 7 ) ; B: D i e n c e p h a l i c DA s y s t e m s ( A l l , A 1 2 , A 1 3 , A 1 4 , and A 1 5 ) ; a f t e r Moore ( 1 9 8 7 ) ; R o t h , W u l f , and D e u t s c h ( 1 9 8 7 ) .  4  cord  5 Autoradiographic  s t u d i e s r e v e a l e d the e x i s t e n c e of b i n d i n g  sites  f o r a v a r i e t y of DA a g o n i s t s and  antagonists within brain  areas  i n n e r v a t e d by DA t e r m i n a l s , such as the o l f a c t o r y  f r o n t a l c o r t e x , caudate-putamen, globus accumbens, bed  nucleus  of the s t r i a  the septum, b a s o l a t e r a l n u c l e i hypothalamus  (Creese,  pallidus,  nucleus  t e r m i n a l i s , medial  of the amygdala, and  Burt, & Snyder, 1976;  bulbs,  nucleus  mediobasal  Kebabian, P e t z o l d , &  Greengard, 1972;  Seeman, Chau-Wong, Tedesco, & Wong, 1975).  Initially,  b i n d i n g s i t e s were thought to r e p r e s e n t  these  s i n g l e , complex r e c e p t o r p r o t e i n . demonstrated at l e a s t two one  Subsequent a n a l y s e s ,  pharmacologically d i s t i n c t  l i n k e d to the s t i m u l a t i o n of a d e n y l a t e  other  e i t h e r not  (Creese,  1983;  suggested  1979).  Seeman, 1980), a more r e c e n t review t h a t DI and state  D2  (Creese,  receptors exist  DI r e c e p t o r s but  (Kebabian,  affinities can be regions  a h i g h - and  i n nanomolar q u a n t i t i e s at D2  types  (e.g.,  proposed  low-affinity  (Tamminga & G e r l a c h ,  (Creese,  receptors  A l l c l a s s e s of DA  antagonist  of r e c e p t o r but with somewhat d i f f e r e n t  l o c a t e d p r e - and  h i g h - and  r e c e p t o r subtypes  a c t s as an a g o n i s t i n micromolar q u a n t i t i e s  B e a u l i e u , & I t o h , 1984).  bind to both  (D2)  1985).  In g e n e r a l , DA at  the  further studies  of t h i s l i t e r a t u r e  i n both  however,  c y c l a s e (DI), and  Although  the e x i s t e n c e of four d i s t i n c t  a  receptors,  l i n k e d or i n h i b i t o r y to cAMP formation  Kebabian & Calne,  of  1987).  Both DI and  p o s t s y n a p t i c a l l y i n major DA  1985), although  preferential sites  l o w - a f f i n i t y subtypes i s s t i l l  D2  receptors  terminal for their  a matter of debate.  6 Several  DA p a t h w a y s ,  mesolimbic/mesocortical incertohypothalamic of  physiological  coordination Zis,  most n o t a b l y t h e m e s o s t r i a t a l  (A10),  (A13, A14),  and b e h a v i o r a l  (Freed & Zee,  & Phillips,  1975),  1986) , p r e p a r a t o r y  Fibiger  1985;  Salamone,  & Phillips,  (Wise,  1982),  1988) ,  learning  (Moore,  concerning  the precise  that  certain than  1988),  of  aspects  role  disrupt  of  that  Evenden, & (Crow,  1976),  DA p l a y s  & Feldon,  although  it  it  in the  However,  affected  by  to  imagine  integration  has been d e m o n s t r a t e d  a r e more s e n s i t i v e  a  exists  in behavior.  is d i f f i c u l t  role  regulation  agreement  processes  1973;  reward  has a l s o g e n e r a t e d  Little  or that  t o DA d i s r u p t i o n  others.  Dopamine and I n c e n t i v e An i m p o r t a n t to  & Fibiger,  motivation  processes  behavioral  behavior  (White,  a l . , 1 9 8 1 ; Weiner  DA a c t i v i t y ,  behavior, of  (Carli,  variety  (Fibiger,  and n e u r o e n d o c r i n e  b r a i n DA s y s t e m s p l a y a s i n g l e  coordination  Phillips,  incentive  controversy.  l a r g e number o f that  initiation  responsiveness  activation  This v a r i e t y  amount o f  treatments  response  (Solomon e t  (Beninger,  substantial  given the  motor  including  1 9 8 6 ; Mogenson & P h i l l i p s ,  attention  1987).  functions,  (Blackburn,  1988),  and  in a  sensorimotor  behaviors  (A12),  have been i m p l i c a t e d  1982),  1987) , g e n e r a l m o t i v a t i o n a l Robbins,  tuberoinfundibular  (A9),  the d i s r u p t i o n  incentive  Motivation  example of d i f f e r e n t i a l of  motivation,  behavioral  sensitivity  DA s y s t e m s comes f r o m t h e a n a l y s i s i n which environmental  stimuli  of  that  have  7 been a s s o c i a t e d initiate Toates,  with biologically  and m a i n t a i n b e h a v i o r 1981; Weingarten,  incentive  motivation  (Craig,  recognizes  1918; K o n o r s k i ,  behaviors, patterns  form of  behaviors  may be c o n t a i n e d  appetitive  t a x o n o m y assumes t h a t incentives  1918).  because a n i m a l s  1972;  stimuli  that  anticipate  or  action a  feeding,  preparatory classes  1982).  other  of  This  primary  anticipatory  the p r e s e n t a t i o n  b a s e d on i n f o r m a t i o n  this  behavior  lead to  s u c h as  (Macphail,  preparatory  of  Preparatory  t h e more g e n e r a l  behaviors  of  are v a r i a b l e  Theoretically,  within  elicit  to  made e a r l i e r  s e c o n d a r y cues a s s o c i a t e d w i t h  c a n come t o  incentive  incentive  or m a t i n g .  or a n t i c i p a t o r y  Bolles,  the d i s t i n c t i o n  consummatory r e s p o n d i n g ,  fleeing,  come  A complementary a n a l y s i s  1967; Woodworth,  fighting,  primary  1968;  s u c h as h o a r d i n g and f o r a g i n g ,  particular  events  and c o n s u m m a t o r y a s p e c t s  made i n r e s p o n s e t o  responses  (Bindra,  1985).  c e n t u r y between p r e p a r a t o r y  important  of  p r o v i d e d by t h e  the  secondary  cues. Although the d i v i s i o n consummatory b e h a v i o r s studies  have shown t h a t  appropriate utilize  DA a n t a g o n i s t s  disrupted (Blundell,  For  those r a t s  to  or  lesions  example,  a number  of  especially  t h e DA r e c e p t o r  food.  1977)  with  the  those  without  Lesions  in rats  antagonist affecting  of mesolimbic  and  of  DA n e u r o n s t o d i s r u p t  hoarding behavior  & Latham,  ingest  open t o d e b a t e ,  manipulations,  by low doses of Strupp,  often  t h e t w o c a n be d i s s o c i a t e d  experimental  transmission.  of  is  between a n t i c i p a t o r y / p r e p a r a t o r y  that DA  c a n be pimozide the  ability  DA n e u r o n s  8 with  6-hydroxydopamine  rats  b u t do n o t  & Stinus,  alter  disrupt  low t o moderate doses of  in rats  (Fibiger,  and i n c r e a s e  the  or  to eat  latency  secondary r e i n f o r c e r s  bouts that  of  the rats  operant  "anhedonia" rewarding food,  receptor  antagonist  made b y r a t s signalled attenuated affect  delivery.  cues,  but food  1985).  al.  (1987)  pimozide  of  the conditioned  these r e s u l t s  mesolimbic  responding  rats  This  with the  confound  of  rather  reduce  they  itself  led to  animals  food  1981),  ability  toward  To c o n t r o l  on c o n d i t i o n e d  to  process of  less  the presence of  stimulus  (CS+)  of  t h e DA  preparatory  Low d o s e s o f  preparatory  between  suggestions  induced a s t a t e  for  food.  preparatory  examined t h e e f f e c t  a meal.  food  was p e r c e i v e d as  conditioned  responses  that  pimozide but d i d  not  t o consume t h e m e a l f o l l o w i n g  its  in contrast  indicated  for  (Tombaugh,  the r a t s '  t h e r e s p o n s e s made  the a b i l i t y  the d e l i v e r y  Thus,  of  a f e e d i n g bout  d i d not n e c e s s a r i l y  of  Similarly,  1 9 7 4 ; Wise & S c h w a r t z ,  made r e p e a t e d c o n t a c t  to a positive  the a b i l i t y  lesions  (Kelley  were c o n f o u n d e d by t h e p r e s e n c e o f  1982,  Blackburn et  1978).  in  begun.  in which the  (Wise,  or  b u t do n o t a f f e c t  however,  by d i s r u p t i n g  response-eliciting  significantly  & Robbins,  initiate  responding.  DA a n t a g o n i s t s  behavior  to  hoarding behavior  instrumental  & Zis,  1979),  In those s t u d i e s ,  Typically,  Smith,  eliminate  once f e e d i n g has  intake  DA a n t a g o n i s t s  Phillips,  Tombaugh, & A n i s m a n ,  eliminate  food or water  1985; Koob, R i l e y ,  DA n e u r o n s d i s r u p t  or  that  to Wise's pimozide  responses  anhedonia affected  hypothesis,  the  preparatory  9 responding  to the e x t e r n a l CS+ d i r e c t l y , without  a f f e c t i n g the  reward v a l u e of the food. Although  the f e e d i n g l i t e r a t u r e c o n t a i n s perhaps the best  examples of the s e n s i t i v i t y of p r e p a r a t o r y responding t o d i s r u p t i o n s of f o r e b r a i n DA systems, t h i s s e n s i t i v i t y i s not limited  to f e e d i n g .  behavior  P r e p a r a t o r y a s p e c t s of one-way  i n r a t s are a t t e n u a t e d  avoidance  by doses of DA a n t a g o n i s t s t h a t  do not a f f e c t subsequent escape responses  (Blackburn,  1989).  summary, i t would appear t h a t DA p l a y s an e q u a l l y important i n both  f e e d i n g and a v o i d i n g : t h a t of p r e p a r i n g an animal  based on d i s t a l cues i n the environment. capable  Although  In role  to act  animals a r e  of l e a r n i n g a s s o c i a t i o n s f o l l o w i n g the a d m i n i s t r a t i o n of  DA a n t a g o n i s t s responses  (Beninger,  1983), they are unable  on the b a s i s of these a s s o c i a t i o n s .  to i n i t i a t e  In c o n t r a s t , when  DA systems are s t i m u l a t e d by DA a g o n i s t s , animals  become more  r e s p o n s i v e t o r e l e v a n t cues i n the environment  (Beninger,  & Phillips,  This  1981; H i l l ,  does not support  1970; Robbins, 1978).  the idea t h a t DA p l a y s an important  consummatory responses  d i r e c t e d a t l o c a l or i n t e r n a l  Hanson,  literature role in cues.  U n f o r t u n a t e l y , our knowledge of the r o l e played by DA i n other motivated  b e h a v i o r s , and i n p a r t i c u l a r , s e x u a l b e h a v i o r , has not  A kept pace with e i t h e r the t h e o r e t i c a l or e m p i r i c a l developments i n the f e e d i n g and avoidance  literature.  Relevance of Dopamine to Sexual The  impetus t o study the involvement  Behavior  of c e n t r a l DA systems  10 i n mammalian sexual and  experimental  performance has  behavior  sources.  comes from a v a r i e t y of  S t i m u l a t i o n of s e x u a l  been r e p o r t e d  anecdotal  arousal  by r e c r e a t i o n a l users  and  of drugs t h a t  s t i m u l a t e DA  pathways or r e c e p t o r s , such as d-amphetamine,  cocaine,  apomorphine ( C a r t e r & Davis,  and  Schneiden & Rees, 1985; useful  Waud, 1933).  i n the treatment of e r e c t i l e  1987).  orgasm or i n h i b i t  aspects  Verberg, & S o l d i n g e r , r e p o r t s , the  precursor  with  lisuride,  the DA  C o n s i s t e n t with  Doherty, Smith, & Klemcke, 1983;  Barwin, 1985;  been receptor  Bowers &  Ruilope  of sexual  et a l . , 1985).  arousal  P a r t of the problem stems from the  c o n t r o l l e d experiments t h a t u t i l i z e d o u b l e - b l i n d  or  function.  to c o n t r o l f o r both placebo  drug with  These procedures  e f f e c t s and  DA  lack of w e l l -  a d m i n i s t r a t i o n procedures or t h a t c o n t r a s t drug e f f e c t s  necessary  Van  f a c i l i t a t e d by DA a g o n i s t s or d i s r u p t e d by  b a s e l i n e assessments of s e x u a l  Svare,  i s f r a u g h t with i n c o n s i s t e n c i e s .  i s not known e x a c t l y what aspects  performance are  with  apomorphine (Bartke,  & Nusimovich, 1981;  However, the human l i t e r a t u r e  has  1-DOPA or the DA and  these  disease,  hyperprolactinemia,  bromocriptine,  Pierini  as  (Kotin, Wilbert,  c o n d i t i o n s , such as Parkinson's  counteracted  antagonists.  t r a n s m i s s i o n , such  arousal  P e t r i e , 1985).  and  Woert, 1972;  ( L a i et a l . ,  a n t i p s y c h o t i c agents, e i t h e r d e l a y  diabetes, renal f a i l u r e ,  agonists  DA  1975;  a l s o proven  l o s s of s e x u a l d e s i r e or a r o u s a l a s s o c i a t e d  c e r t a i n medical  It  dysfunction  of s e x u a l  1977;  Hollister,  Apomorphine has  In c o n t r a s t , drugs t h a t i n h i b i t  the major t r a n q u i l i z e r s and  1976;  are  any p r e e x i s t i n g  11 sexual dysfunction.  In a d d i t i o n , assessments of s e x u a l f u n c t i o n  are made almost e n t i r e l y on the b a s i s of p a t i e n t s e l f - r e p o r t ; few s t u d i e s have examined p h y s i o l o g i c a l measures of s e x u a l  arousal  f o l l o w i n g the a d m i n i s t r a t i o n of DA a g o n i s t s or a n t a g o n i s t s and none have attempted t o measure s e x u a l behavior A second problem i n the human l i t e r a t u r e conceptual behavior  r e l a t i o n s h i p of d i f f e r e n t aspects  and t h e t e r m i n o l o g y  i n v o l v e s the of human s e x u a l  used t o d e s c r i b e them.  t h e o r i e s of human s e x u a l behavior conceptually separate,  directly.  Early  emphasized the r o l e of two  but p h y s i o l o g i c a l l y  integrated, substrates  of s e x u a l a r o u s a l and performance (e.g., M o l l , 1897; K r a f f t Ebing,  1929; E l l i s ,  1938); however, each used d i f f e r e n t terms and  operational d e f i n i t i o n s .  Unfortunately,  to plague the human l i t e r a t u r e .  Although  t h i s problem  continues  attempts have been made  e m p i r i c a l l y to s p e c i f y conceptually d i s t i n c t  aspects  of the human  s e x u a l response c y c l e (e.g., Kaplan, 1974; Masters & Johnson, 1966), and t o d e f i n e s e x u a l d i s o r d e r s and d y s f u n c t i o n s w i t h i n an empirically-derived  framework  (e.g., DSM-IIIR, American  P s y c h i a t r i c A s s o c i a t i o n , 1987), a m a j o r i t y of p u b l i s h e d h i s t o r i e s use i l l - d e f i n e d human s e x u a l  and outdated  terminology  to describe  behavior.  For example, the DSM-IIIR d i v i d e s the human s e x u a l cycle  case  response  i n t o four phases: the a p p e t i t i v e phase ( c o n s i s t i n g of  f a n t a s i e s about, and a d e s i r e t o engage i n , s e x u a l a c t i v i t y ) , the excitement  phase ( c o n s i s t i n g of the s u b j e c t i v e and p h y s i o l o g i c a l  changes t h a t accompany s e x u a l excitement  and p l e a s u r e ) , the  orgasm phase ( c o n s i s t i n g of the s u b j e c t i v e and p h y s i o l o g i c a l changes t h a t accompany the peaking  of s e x u a l p l e a s u r e ) , and the  r e s o l u t i o n phase ( c o n s i s t i n g of the s u b j e c t i v e and p h y s i o l o g i c a l changes f o l l o w i n g orgasm).  C o n s i s t e n t with these phases, the  DSM-IIIR d i s t i n g u i s h e s among s e x u a l d e s i r e d i s o r d e r s ( i n which i n d i v i d u a l s experience of s e x u a l  e i t h e r a p e r s i s t e n t and r e c u r r i n g absence  f a n t a s i e s and d e s i r e f o r s e x u a l a c t i v i t y or an extreme  a v e r s i o n t o , or avoidance o f , g e n i t a l s e x u a l a c t i v i t y ) , a r o u s a l d i s o r d e r s ( i n which i n d i v i d u a l s experience i n a b i l i t y t o a t t a i n or m a i n t a i n excitement,  sexual a c t i v i t y ) , experience  e i t h e r an  p h y s i o l o g i c a l aspects  or a lack of s u b j e c t i v e excitement orgasm d i s o r d e r s ( i n which  sexual  of s e x u a l  or p l e a s u r e  during  individuals  e i t h e r a d e l a y i n , or the absence o f , orgasm f o l l o w i n g  normal s e x u a l excitement,  or premature e j a c u l a t i o n d e r i v e d  from  minimal s e x u a l s t i m u l a t i o n ) , and s e x u a l p a i n d i s o r d e r s ( i n which i n d i v i d u a l s experience  e i t h e r r e c u r r e n t or p e r s i s t e n t g e n i t a l  p a i n b e f o r e , d u r i n g , or a f t e r s e x u a l an  i n t e r c o u r s e , or  i n v o l u n t a r y spasm of the outer t h i r d  i n t e r f e r e s with s e x u a l a c t i v i t y ) .  of the vagina  vaginismus, that  D e s p i t e the wealth of  i n f o r m a t i o n t h a t c o u l d be d e r i v e d from the a p p l i c a t i o n of t h i s taxonomy, many c l i n i c i a n s c o n t i n u e  t o use terms l i k e  "potency" t o d e s c r i b e v a r i o u s processes a r o u s a l , and c a p a c i t y f o r orgasm. to know e x a c t l y what aspects affected  by drugs,  " l i b i d o " and  of s e x u a l d e s i r e ,  As a r e s u l t ,  i t is difficult  of human s e x u a l behavior are  i n p a r t i c u l a r , DA a g o n i s t s and a n t a g o n i s t s .  In r e c e n t y e a r s ,  i n t e r e s t has grown i n the use of animal  models to study drug e f f e c t s on s e x u a l  behavior.  The  e x p e r i m e n t a l c o n t r o l o f f e r e d by an animal model circumvents many of the problems i n h e r e n t equally  i n the use of human s u b j e c t s .  important advantage i s t h a t a l a r g e l i t e r a t u r e e x i s t s on  the b i o c h e m i c a l ,  pharmacological,  drugs i n l a b o r a t o r y a n i m a l s .  and b e h a v i o r a l  This  i n other  behavioral  p r o p e r t i e s of  l i t e r a t u r e can be used t o  compare the e f f e c t s of drugs on s e x u a l effects  An  behavior with  paradigms, and can help  their determine  mechanisms of a c t i o n . The  e f f e c t s of DA a g o n i s t s  and a n t a g o n i s t s  behavior have been s t u d i e d most e x t e n s i v e l y reviewing  these d a t a ,  theoretical  on animal  i n male r a t s .  sexual Before  s e v e r a l important m e t h o d o l o g i c a l and  i s s u e s about s e x u a l  motivation  must be  considered.  D e s c r i p t i o n of the Sexual Behavior of Male Rats A n a l y s i s of C o p u l a t o r y Behavior The  sexual  behavior of male r a t s depends upon the i n t e g r a t e d  a c t i v i t y of a v a r i e t y of c e n t r a l and p e r i p h e r a l n e u r a l The  b a s i c components of the c o p u l a t o r y  pattern,  systems.  including  o r i e n t a t i o n toward a r e c e p t i v e female, p r e c o p u l a t o r y  approach and  i n v e s t i g a t i o n of the female, p e n i l e e r e c t i o n , mounting, p e l v i c thrusting, vaginal urethra,  i n t r o m i s s i o n , seminal emission i n t o the  e j a c u l a t i o n , and a p o s t e j a c u l a t o r y  r e f r a c t o r y phase, a r e c o n t r o l l e d by n e u r a l cord  i n t e r v a l or centers  and b r a i n , each of which i n t e r a c t c o n t i n u o u s l y  copulation.  This pattern  of c o p u l a t i o n ,  i n the s p i n a l during  from p u r s u i t and  inspection  of  the  intromissions, ejaculatory interval,  female,  and f i n a l l y  series.  Studies  of  the percentage ejaculations, ejaculation,  or P E I ) .  calculated  ultrasonic  1976).  of  to  (III,  first  1976;  intromissions)  (the  phases.  This period  is  (Barfield  either  mounts  of  ratio  mounts  Some s t u d i e s  t h e PEI  into  ejaculation,  continues 1975;  for  inactive,  to a variety  of  (IR, with use  its male  approximately  Sachs & B a r f i e l d ,  the absolute r e f r a c t o r y  males are t y p i c a l l y  or  inter-  intromission  after  & Geyer,  finite  ejaculation  reported.  that  precede  intromission,  s u c h as t h e  to divide  considered  hyposensitive  first  as t h e  Shortly  that  and  postejaculatory  and t h e  are also  report  displayed during a  intromissions/number  techniques  t h e PEI  generally  intromissions,  mount,  calculated  a 22 kHz v o c a l i z a t i o n  it  male r a t s  Secondary measures,  recording  dramatically  five  exhausted  Sachs & B a r f i e l d ,  of  ejaculation  intromission)  because d u r i n g  1956;  latency to r e i n i t i a t e  interval  75% o f  another  mounts and i n t r o m i s s i o n s  latencies  and r e l a t i v e  emit  for  b e f o r e becoming s e x u a l l y  ejaculations  as t h e number o f  and w i t h o u t  t o as an  postejaculatory  t h a t d i s p l a y mounts,  following  latency/number  50% t o  the  and t h e  intromission  rats  rats  t h e number o f  intromissions  referred  initial  the sexual behavior  t h e number o f  ejaculation,  mounts,  1988).  of  period,  interval,  series  is  of  resumes c o p u l a t i o n  1956; L a r s s o n ,  Sachs & M e i s e l ,  initiation  ejaculation,  t h e male t y p i c a l l y  (Beach & J o r d a n ,  absolute  the  Following the  t o seven e j a c u l a t o r y  testing  to  and  external  phase  are stimuli,  including  shock  vocalizations  (Pollak  cease,  & Sachs,  1988).  w i t h shock  During t h i s  d i s p l a y more i n t e r e s t anogenital  relative  in the  investigation of  copulation.  drug e f f e c t s  on t h e s e x u a l b e h a v i o r  through several  ejaculatory  Gray,  Davis,  & Holmes,  & Dewsbury,  & Gorzalka,  Analysis  Sexual  of  or  to sexual Bitran,  & Rinne,  intromission  the evaluation  of  examine  assess  several  series  included a l l  with special latencies  ejaculation,  status  the  effects  exhaustion  Pehek,  Warner,  1971; M i l l e r  sexual motivation  1976). III,  with the of  (e.g. Band  & Baum,  in  female r a t .  b e i n g g i v e n t o mount the  first  a l t h o u g h b o t h may c o n s i s t components  The number o f  ways  These  behaviors and copulatory  of  (Cherney & Bermant, intromissions  and t h e e j a c u l a t i o n  the  behavior  the copulatory  because t h e y r e f l e c t  and p e r f o r m a n c e  Sachs & B a r f i e l d ,  and  i n two f u n d a m e n t a l l y d i f f e r e n t  interaction  made b y t h e m a l e ,  motivational  the  that  have e x a m i n e d d r u g  series  of  leads to  a p p r o a c h has been t o a n a l y z e measures o f  above,  males  1987).  m e a s u r e s have g e n e r a l l y  contact  ejaculatory  1974; H u l l ,  p e r f o r m e d by t h e male i n  listed  others  has been a p p r o a c h e d  The f i r s t  (Sachs &  phase,  finally  and  Motivation  Traditionally, male r a t  that  o f male r a t s  first  1986; Hyyppa, L e h t i n e n ,  1987; Pfaus  pinch  A l t h o u g h most s t u d i e s  t h e s e measures t h r o u g h t h e interval,  behaviorally  refractory  and p u r s u i t  postejaculatory  or t a i l  22 kHz  f e m a l e and b e g i n a p a t t e r n  reinitiation  of  Once t h e  m a l e s become more a c t i v e  c a n be i n d u c e d t o c o p u l a t e Meisel,  1975).  1970  preceding  l a t e n c y have a l s o  been  viewed as measures of s e x u a l m o t i v a t i o n  that r e f l e c t  either  the  r a t e of c o p u l a t i o n or the amount of g e n i t a l s t i m u l a t i o n r e q u i r e d for  ejaculation.  "enforced  For example, L a r s s o n  interval effect",  lengthening  (1956) d e s c r i b e d  i n which an  the  experimenter-imposed  of the I I I (achieved by p r e s e n t i n g a s e x u a l l y  r e c e p t i v e female to a male at i n t e r v a l s longer than the male's normal I I I ) reduced ejaculation.  the number of i n t r o m i s s i o n s r e q u i r e d f o r  Larsson  noted  t h a t the  made the males appear " r e s t l e s s and  interruption in copulation a p p a r e n t l y e x c i t e d " (p.  In a d d i t i o n , c o p u l a t i o n would resume immediately female.  These o b s e r v a t i o n s  121).  upon replacement  of  the  suggest  t h a t the i n t e r r u p t i o n  of  c o p u l a t i o n i n c r e a s e s s e x u a l a r o u s a l and  reduces the amount of  penile s t i m u l a t i o n required for e j a c u l a t i o n . itself and  Barfield  thus to  appears to be r e l a t e d  Likewise,  the I I I  i n v e r s e l y to a r o u s a b i l i t y .  Karen  (1975) demonstrated t h a t males with s h o r t I l l s  a f a s t e r c o p u l a t o r y r a t e ) achieved  s e x u a l exhaustion  than males with  (and  more e j a c u l a t i o n s p r i o r  long I l l s .  F i n a l l y , some  s t u d i e s have used the p e r s i s t e n c e of mounting behavior  following  p e n i l e a n e s t h e s i a or c a s t r a t i o n as a measure of s e x u a l  motivation  (e.g., Malmnas, 1973;  Dorsa & Smith, 1980).  There are s e v e r a l problems i n the derived  from t h i s  first  approach.  i n t e r p r e t a t i o n of  Behaviors  performed by  male i n i n t e r a c t i o n with the female can be confounded by l e v e l of s e x u a l r e c e p t i v i t y . c a s t r a t i o n g e n e r a l l y precludes behavior.  Although  The  use  data the her  of p e n i l e a n e s t h e s i a  the f u l l  e x p r e s s i o n of  or  copulatory  each measure of c o p u l a t o r y behavior  may  be  17 sexually motivated measures t o specify  infer  by d e f i n i t i o n ,  sexual motivation  the r e l a t i v e  components of aspects  of  t h e use o f  contribution  results  of  each.  s e x u a l m o t i v a t i o n may e x i s t  copulatory  behavior  some o r a l l  of  in a f a i l u r e  to  Indeed, that  distinct  prime  (Sachs & B a r f i e l d ,  different  1976).  The s e c o n d a p p r o a c h has been t o a n a l y z e b e h a v i o r s b y t h e male e i t h e r  t o g a i n access t o ,  sexually receptive  female r a t .  performance running  in obstruction  (Sheffield,  (Whalen,  1961),  bar-pressing Stacey,  crossing  behavior  Sachs, Macaione, interpretation  of  & Fagy,  (Moss,  Kostarczyk,  Dewsbury,  Taylor,  & Malagodi,  second approach  is  often  historical  teaching animals  instrumental  or  the  of  responses  sexual  that  behavior,  inferences  approach,  (1956)  situations rates  nature  of  natural  investigators  in particular  t o make g e n e r a l  is  Perhaps  have no many  the  baseline  the time-consuming  copulatory behavior,  latencies,  some o f  and t h e e s t a b l i s h m e n t  precedent,  &  Although  extremely time-consuming.  i n the e x p r e s s i o n of  use m e a s u r e s o f  elegant,  and  1971;  from t h i s  and t h e o r e t i c a l l y  alley  1924),  of data d e r i v e d  of  intromission  grids  a  learning  1956).  artificial  place  straight  Schwartz,  are r e l a t i v e l y  because of  1927),  of,  included  1974;  straightforward  performance  Fray,  Taylor,  have  1 9 5 1 ) , maze  electrified  (Everitt,  1987; J o w a i s a s ,  (Warner,  & Backer,  performed  in anticipation  Such b e h a v i o r s  boxes  Wulff,  or  these  t h e mount about  and  sexual  motivation. Based on t h e factor  t h e o r y of  first  sexual motivation  Beach that  proposed a t w o -  essentially  restated  the  18 d i s t i n c t i o n noted aspects  above between a n t i c i p a t o r y and consummatory  of b e h a v i o r .  He suggested  consummation of c o p u l a t o r y behavior independent m o t i v a t i o n a l p r o c e s s e s . the  t h a t the i n i t i a t i o n  were under the c o n t r o l of two The f i r s t  process,  called  "sexual a r o u s a l mechanism" was thought t o o r i e n t the male  toward the female and i n i t i a t e mounts. called to  and  The second  process,  the " i n t r o m i s s i o n and e j a c u l a t i o n mechanism" was  d r i v e the s t e r e o t y p e d  culminates  thought  p a t t e r n of p e n i l e i n t r o m i s s i o n s t h a t  in ejaculation.  More r e c e n t l y , Sachs (1978) p u b l i s h e d  the r e s u l t s of a f a c t o r a n a l y s i s of t e n measures of s e x u a l behavior  performed by the male i n i n t e r a c t i o n with the female.  From the r e s u l t s of t h i s a n a l y s i s , Sachs proposed the e x i s t e n c e of  at l e a s t  four independent processes  of  s e x u a l behavior  by the male r a t .  c h a r a c t e r i z e d by f a c t o r s c a l l e d  u n d e r l y i n g the performance  These processes  the i n i t i a t i o n  were  f a c t o r , the  c o p u l a t o r y r a t e f a c t o r , the h i t r a t e (the percentage of mounts resulting  i n i n t r o m i s s i o n ) , and the i n t r o m i s s i o n count.  Although  Sachs' approach r e t a i n e d a d i s t i n c t i o n between p r e p a r a t o r y and consummatory aspects consummatory aspect  of c o p u l a t o r y b e h a v i o r , into three  i n t e r a c t i v e , processes intromission  i t s e p a r a t e d the  independent, but o b v i o u s l y  ( c o p u l a t o r y r a t e f a c t o r , h i t r a t e , and  count).  One of the most complex models of s e x u a l m o t i v a t i o n comes from the work of Toates  (Toates, 1986; Toates & O'Rourke, 1978).  T h i s model assumes t h a t s e x u a l m o t i v a t i o n both  or a r o u s a l depends upon  the magnitudes of the e x t e r n a l i n c e n t i v e and the i n t e r n a l  s t a t e of s e x u a l copulatory  arousability.  behavior  cascade, from the a f f e c t i n g the motivational  Although i n d i v i d u a l measures of  are viewed as forming p a r t of an  first  mount to e j a c u l a t i o n , with  likelihood  of subsequent events,  f a c t o r s are nested  example, blood  c o n t r o l s the t h r e s h o l d  of a r o u s a l t h a t must  i n t r o m i s s i o n s are  c o p u l a t i o n has  been i n i t i a t e d , however, blood  appear to p l a y a d e c i s i v e r o l e .  as the g e n i t a l s t i m u l a t i o n d e r i v e d a c t i v e p u r s u i t of the  discusses  initiated.  be  Once  hormone l e v e l s  Other i n t e r n a l events,  do such  from each i n t r o m i s s i o n and  i n sexual the  a r o u s a l or a r o u s a b i l i t y .  importance of u s i n g female as  Although Toates  instrumental  behavior  i n d i c e s of m o t i v a t i o n , bar  press  or  he notes t h a t  f o r a primary  the  sexual  (e.g., a r e c e p t i v e female) i s low r e l a t i v e to r a t s  r e i n f o r c e d with  food  (instrumental  behavior  i s dependent upon  both the nature of the task  and  t h a t c o n s t i t u t e the g o a l ) .  Toates, however, makes no attempt  instrumental  the s i z e of the d i s c r e t e u n i t s  responding f o r a s e x u a l  reward w i t h i n  framework of the model system he proposes f o r s e x u a l It  the  female, appear to s e n s i t i z e an e j a c u l a t i o n  r a t e at which male r a t s w i l l  place  the  E j a c u l a t i o n , i n t u r n , d e s e n s i t i z e s the pathways  p u r s u i t of the  incentive  This a l t e r s  sexually-arousing  mounts and  involved  For  hormone l e v e l s c o n t r i b u t e to s e x u a l a r o u s a b i l i t y  reached before  mechanism.  behavior  w i t h i n c e r t a i n measures.  response t h a t male r a t s make towards a  not  each  potential  by a l t e r i n g the e x c i t a b i l i t y of c e r t a i n neurons.  i n c e n t i v e and  intricate  i s not c l e a r i n T o a t e s ' model what aspects  of  to  the  motivation.  sexual  20 m o t i v a t i o n might be i n f e r r e d what a f f e c t such responding  from i n s t r u m e n t a l responding, nor might have on the subsequent  e x p r e s s i o n of c o p u l a t i o n . In summary, elements of the second approach d e s c r i b e d above have not been i n t e g r a t e d w i t h i n major t h e o r e t i c a l models of sexual motivation  or b e h a v i o r .  T h i s makes i t d i f f i c u l t t o  e s t a b l i s h a c l e a r d i s t i n c t i o n between a n t i c i p a t o r y or p r e p a r a t o r y sexual behaviors  and consummatory s e x u a l b e h a v i o r s  e m p i r i c a l evidence.  As noted  based on  p r e v i o u s l y , both mount and  i n t r o m i s s i o n l a t e n c i e s and the PEI (measures t h a t c o n s t i t u t e Beach's s e x u a l a r o u s a l mechanism and Sachs' i n i t i a t i o n  factor)  can be confounded by the degree of s e x u a l r e c e p t i v i t y of the female. to  I t i s i n c o r r e c t t o use mount or i n t r o m i s s i o n l a t e n c i e s  i n f e r a n t i c i p a t o r y or p r e p a r a t o r y s e x u a l m o t i v a t i o n  both can be c o n s i d e r e d behaviors  consummatory a c t s .  because  Unfortunately,  other  t h a t males may engage i n p r i o r t o mounting the female  (e.g., grooming, s e a r c h i n g , and p u r s u i t ) are r a r e l y r e p o r t e d i n assessments of s e x u a l behavior important  s e x u a l l y motivated  although  they may c o n s t i t u t e  p r e p a r a t o r y or a n t i c i p a t o r y  behaviors. S e p a r a t i n g s e x u a l behavior  i n t o a n t i c i p a t o r y / p r e p a r a t o r y and  consummatory components may be a v a l u a b l e h e u r i s t i c f o r i d e n t i f y i n g the n e u r a l mechanisms t h a t c o n t r o l p a r t i c u l a r of  sexual behavior.  S e v e r a l s t u d i e s have noted  aspects  t h a t the a c t i v e  p u r s u i t of a s e x u a l l y r e c e p t i v e female does not n e c e s s a r i l y result  in copulation.  For example, c a s t r a t e d male r a t s w i l l  maintain a high rate receptive display  female's  copulatory  Treatment w i t h medial  behavior  pursuit  the  the sexual (1987),  anogenital behavior  area  copulatory  demonstration  precopulatory  female of  intact.  of  copulatory  on r a t e s  of  female.  Had mount o r  & Beran,  lesions  behavior  of  intromission  latencies  sexual behavior  Although  it  is  possible  a r e d r i v e n b y t h e same m e c h a n i s m t h a t  mounting,  but are simply  surgical  or c h e m i c a l  possible  that  presence, behavior  treatments  behaviors  sexually receptive  female,  precopulatory  initiates particular  above,  or  otherwise  it  is  from the  in anticipation  initiation  f o r a g i n g c a n be d i s s o c i a t e d  Thus s e v e r a l m o t i v a t i o n a l consummatory s e x u a l  eliminated  mechanism or  that  to the  described  there  also  p e r f o r m e d b y t h e male t o g a i n a c c e s s t o  may be d i s s o c i a t e d much l i k e  sensitive  effect  only  the treatments  behaviors  less  area  in those s t u d i e s ,  a sexual arousal  by d i s r u p t i n g  in  receptive  been t h e  copulatory  factor.  and  Stacy  i n t h o s e m a l e s b u t had no  that  an i n i t i a t i o n  and  the medial p r e o p t i c  w o u l d have been r e a s o n t o s u g g e s t behavior  male  convincing  t o g a i n access t o a s e x u a l l y  "preparatory"  the  investigation  t h e most  of  from  c o m p o n e n t s may c o n v e r g e t o  behaviors.  to  1976).  of  eliminate  was made b y E v e r i t t  lesions  bar-pressing  a  and c o n s u m m a t o r y d i s t i n c t i o n  male r a t s  i n which c e r t a i n  measures of  Perhaps  or  1966)  leave precopulatory  of  t h e y have c e a s e d  Hlinak,  1981)  & Larsson,  a preparatory  behavior  eliminated  area long a f t e r  (Meyerson,  (Heimer but  investigation  (Madlafousek,  o p i o i d drugs  preoptic  of  of  of  her  copulatory feeding. induce  a  T h i s s e c t i o n has  o u t l i n e d some of the t h e o r e t i c a l  t h a t must be c o n s i d e r e d motivation DA  when making i n f e r e n c e s about the  of male r a t s .  i n f e e d i n g and  issues  Although  sexual  the l i t e r a t u r e on the r o l e of  avoidance behavior  makes r e l a t i v e l y  clear  d i s t i n c t i o n s between a n t i c i p a t o r y / p r e p a r a t o r y b e h a v i o r s  and  consummatory b e h a v i o r s ,  behavior  the l i t e r a t u r e on DA and  sexual  does not.  T h i s makes i t d i f f i c u l t  treatments  t h a t e i t h e r enhance or d i s r u p t DA t r a n s m i s s i o n w i t h i n  a more g e n e r a l t h e o r e t i c a l  Role  of DA  s e x u a l behavior  Behavior  of Male Rats: A Review  of the neuropharmacology of DA  of male r a t s conclude  i n the  t h a t e l e v a t e d DA  s e r v e s to i n c r e a s e s e x u a l a r o u s a l i n the presence of incentive stimuli Zemlan, 1981; taken  (see e.g.,  Bitran & Hull,  Sachs & M e i s e l , 1988).  from s t u d i e s u s i n g both  of DA a g o n i s t s or a n t a g o n i s t s , f i b e r s or t e r m i n a l s .  systemic  of s e x u a l  the e f f e c t s of p h a r m a c o l o g i c a l  l e s i o n s of DA  t e r m i n a l r e g i o n s on male s e x u a l b e h a v i o r , DA and  i t s metabolites  and  DA  this  o f t e n c o n t r o v e r s i a l r o l e of  performance aspects  neurochemical  is generally  central administration  with DA a g o n i s t s or a n t a g o n i s t s on male s e x u a l e l e c t r o l y t i c and  appropriate  Crowley &  T h i s evidence and  activity  i n a d d i t i o n to l e s i o n s of major  l i t e r a t u r e r e v e a l s a complex and  T h i s s e c t i o n reviews  1987;  However, a c a r e f u l r e a d i n g of  i n both m o t i v a t i o n a l and  of  framework.  i n the Sexual  Numerous reviews  to p l a c e the e f f e c t s  DA  behavior.  treatment  behavior,  pathways  and  ex v i v o a n a l y s e s  f o l l o w i n g p e r i o d s of c o p u l a t i o n .  of  23 Effect  of  DA a g o n i s t s  Systemic apomorphine, lisuride  administration  of  a variety  N-n-propyl-norapomorphine,  and p e r g o l i d e ,  partial  3-PPP,  release  d-amphetamine,  promoter  active  required or,  sexual arousal  male r a t s for  either  1984a,b; Benelli White,  Ahlenius, & Ferrari,  Pleim,  et a l . ,  Foreman & H a l l , Fratta,  & Gessa,  & Gessa, 1975).  males  copulatory  (Dallo,  Fiacco,  Lekka,  & Gessa,  1966;  1987; C l a r k ,  & Phillips,  Baggio,  Benassi-  Barfield, & Davidson,  & Mangiafico,  1975;  1987;  have been r e p o r t e d  & Knoll,  1986; T a g l i a m o n t e , sexually et  al.,  Mereu,  & Soulairac,  d-amphetamine,  intact,  1985;  Napoli-Farris,  Soulairac  in either  (Bartke  & Larsson,  Smith,  behavior  intact,  latency,  Pellegrini-Quarantotti,  and l i s u r i d e ,  males  generally  intromissions  1982;  Cagiano,  (in  sexually  (Ahlenius  Stafanick,  1981; F e r r a r i ,  1974),  hyperprolactinemic  intact,  t h e DA  1-DOPA  inhibitor),  & Svensson,  1-DOPA, a p o m o r p h i n e ,  bromocriptine  stimulate  Bignami,  1984; P a g l i e t t i ,  1978; Pfaus  B-HT 9 2 0 ,  t h e number o f  1 9 8 7 ; Gessa & T a g l i a m o n t e ,  Similarly,  ergots  in  and LY  the  by d e c r e a s i n g t h e e j a c u l a t i o n  Engel, Larsson,  & Cuomo,  1983; F a l a s c h i  and b e h a v i o r  b y d e c r e a s i n g t h e PEI  1979;  of  and t h e DA p r e c u r s o r  by d e c r e a s i n g  ejaculation,  i n some c a s e s ,  isomer  decarboxylase  derivative  quinpirole  the azepine d e r i v a t i v e  combination with a peripheral facilitates  (+)  s u c h as  derivatives  benzazepine  ergolines  1 6 3 5 0 2 , t h e a m i n o i n d a n e RDS-127, t h e phenylpiperidine  DA a g o n i s t s ,  the ergot  the DI s e l e c t i v e  SKF 3 8 3 9 3 ; t h e D 2 - s e l e c t i v e  of  and  the  to  sexually Fratta,  inactive Del  inactive 1983),  intact,  sexually  inactive Kohler,  males w i t h & Ross,  lesions  1982),  subthreshold  Fernandez,  1989; Malmnas,  quinpirole  the medial p r e o p t i c  and s e x u a l l y  or w i t h o u t  agonist  of  testosterone 1973,  of  e.g.,  exert  their  effects  these  metoclopramide,  effects  et a l . ,  facilitate seminal  the display  1983; Pehek, that  in  et  al.,  of  either  proportion  of  disruption  may o c c u r  h i g h doses of  by d e l a y i n g  rats  that  competing s t e r e o t y p y  active  facilitate  rats,  inactive  penile  and s t i m u l a t e  rats,  Tagliamonte also  (Clark  1988a),  or  copulatory  et  and al.,  effects  DA  disrupt  by d e c r e a s i n g behavior.  DA a g o n i s t s  the  This induce  responses.  Although these data suggest activity  males  DA a g o n i s t s  because h i g h doses of  reverse  s u c h as e r e c t i o n  & Hull,  ejaculation  initiate  the  1976;  reversed with c e n t r a l l y - a c t i n g  Finally,  copulation  Bazzet,  to  pimozide,  o r RDS-127  reflexes  Some  centrally,  domperidone,  sexually active  Thompson, E a t o n ,  antagonists.  1987).  but not  1 9 8 1 ; Malmnas,  apomorphine  penile  intact,  are s e l e c t i v e l y  the  antagonists  antagonist  with  selective  to abolish  and h a l o p e r i d o l ,  Low d o s e s o f  emission  The D2  behavior  DA r e c e p t o r  DA r e c e p t o r  (Falaschi  1974).  males  (Agmo &  (Cagiano e t a l . ,  on male c o p u l a t o r y  peripherally-acting  (Hansen,  a p o m o r p h i n e and 1-DOPA, a r e assumed  because t h e c e n t r a l l y - a c t i n g sulpiride,  1977).  has a l s o been r e p o r t e d  22 kHz v o c a l i z a t i o n  castrated  replacement  1976,  postejaculatory these drugs,  inactive  area  some o f  that  reflexes  increases  and e j a c u l a t i o n  copulatory  the e f f e c t s  moderate  activity  in  in  i n DA  sexually  sexually  are c o n t r o v e r s i a l .  For  25 example,  some s t u d i e s  on t h e c o p u l a t o r y (Ahlenius, Pfaus with  behavior  intact,  of  bromocriptine  sexually active  & Svensson,  unpublished  observations),  testosterone  replacement  (Agmo & F e r n a n d e z ,  that  rather  than decrease,  1974).  In a d d i t i o n ,  some DA r e c e p t o r is  inactive (Baggio  by p r e t r e a t m e n t 1984b;  (e.g.,  the  1983). ergots)  t h a n t h e DA s u b t y p e s .  males  whereas  increase, Gray e t  al.,  ejaculation  induced  by  LY-141865,  and RDS-  w i t h DA a n t a g o n i s t s  & Smith,  1986).  by l i s u r i d e  in  Unfortunately,  of  T h i s makes a s s e s s m e n t s  the  haloperidol  some o f  bind to a v a r i e t y  However, sexually  c a n be r e v e r s e d b y a h i g h d o s e o f  & Ferrari,  t h e DA a g o n i s t s  receptors of  other  receptor  questionable.  Another  major  agonists  is  terminal  regions  that  those s t u d i e s  problem w i t h the systemic  administration  t h e y may b i n d t o DA r e c e p t o r s simultaneously.  to determine  mediate the e f f e c t s examined t h e e f f e c t s S v e n s s e n and Hansen intrathecal  Clark  1971;  (e.g.,  lisuride,  of mounting behavior  rats  selectivity  (e.g.,  of  1989),  1-DOPA  1-DOPA  al.,  or c a s t r a t e d  latency  facilitation  agonists  & Larsson,  facilitation  low doses of  the e j a c u l a t i o n the  not reversed  (Ahlenius  tested  relatively  or  males  1 9 8 2 ; Hyyppa e t  & Phillips,  report  ug)  no e f f e c t  of  Engel, Larsson,  others  127)  report  of of  Thus  whether  those drugs. central  it  is  in several  impossible  particular To d a t e ,  two groups  (1984)- f o u n d no s i g n i f i c a n t  administration  of  of  t o t h e s u b a r a c h n o i d s p a c e on t h e c o p u l a t o r y  regions have  DA a g o n i s t s .  effect  a range of doses of  DA  from  DA t e r m i n a l  administration  o f DA  of  DA ( u p t o  behavior  of  400  26 i n t a c t , s e x u a l l y a c t i v e r a t s , i n d i c a t i n g t h a t s p i n a l DA t e r m i n a l s were not important f o r the r e g u l a t i o n of c o p u l a t o r y DA.  behavior by  However, i n t h a t study a 400 ug dose of DA i n f u s e d  i n t o the  l a t e r a l v e n t r i c l e s s i g n i f i c a n t l y decreased the number of intromissions/min,  an e f f e c t c o n s i s t e n t with the decreased number  of i n t r o m i s s i o n s  t y p i c a l l y observed with s y s t e m i c  of DA a g o n i s t s .  T h i s suggested t h a t s u p r a s p i n a l  responsible  f o r the modulation of c o p u l a t o r y  administration s i t e s alone were  behavior by DA  agonists. A comprehensive s e r i e s of experiments was conducted by H u l l et a l . (1986) i n which apomorphine was i n f u s e d u n i l a t e r a l l y e i t h e r the medial p r e o p t i c area accumbens, l a t e r a l  (MPOA), caudate-putamen, nucleus  septum, or l a t e r a l v e n t r i c l e of i n t a c t ,  sexually active rats.  I n f u s i o n of the lowest dose i n t o the  v e n t r i c l e decreased the t o t a l number of e j a c u l a t i o n s , the  I I I (meaning t h a t  ug) i n f u s e d  increased  i t slowed the r a t e of c o p u l a t i o n ) , and  decreased the number of i n t r o m i s s i o n s . 2.0  into  Two higher  doses  i n t o ^either the v e n t r i c l e or the MPOA  the t o t a l number of e j a c u l a t i o n s , i n c r e a s e d  (0.5 and  increased  the i n t r o m i s s i o n  r a t i o , , and decreased the I I I , the e j a c u l a t i o n l a t e n c y , and t h e PEI.  Although the h i g h e s t  dose i n f u s e d  i n t o the nucleus  accumbens decreased t h e i n t r o m i s s i o n l a t e n c y , t h i s e f f e c t was of borderline s t a t i s t i c a l effect  on c o p u l a t o r y  significance.  F i n a l l y , apomorphine had no  behavior f o l l o w i n g i n f u s i o n s i n t o e i t h e r the  caudate-putamen or l a t e r a l septum. MPOA as an important s i t e  These r e s u l t s i m p l i c a t e d the  i n the r e g u l a t i o n of male  sexual  27 behavior by DA a g o n i s t s . Subsequent s t u d i e s by H u l l ' s group have shown t h a t t h e effect  of apomorphine i n f u s i o n s i n t o the MPOA on male  behavior can be r e v e r s e d  with t h e DA a n t a g o n i s t c i s - f l u p e n t h i x o l  (Pehek e t a l . , 1988c), and t h a t apomorphine i n c r e a s e s r e f l e x e s when i n f u s e d nucleus  copulatory  penile  i n t o e i t h e r t h e MPOA or p a r a v e n t r i c u l a r  (Pehek, Thompson, & H u l l , 1988b).  Apomorphine  i n t o t h e p a r a v e n t r i c u l a r nucleus a l s o i n c r e a s e d  infusions  t h e number of  seminal emissions i n t h a t study, an e f f e c t not observed i n f u s i o n of apomorphine i n t o t h e MPOA. the p o p u l a t i o n s  of DA r e c e p t o r s  following  These data suggest  that r e g u l a t e  that  p e n i l e r e f l e x e s and  seminal e m i s s i o n may have s e p a r a t e a n a t o m i c a l l o c a l i z a t i o n s . contrast al.  t o t h e r e s u l t s of Svenssen and Hansen  (1988b) a l s o r e p o r t e d  apomorphine  that  In  (1984), Pehek e t  i n t r a t h e c a l a d m i n i s t r a t i o n of  (50 ug) t o the lumbosacral but not m i d t h o r a c i c  s e c t i o n s of t h e s p i n a l cord decreased the number of i n t r o m i s s i o n s and  increased  the III i n i n t a c t , s e x u a l l y a c t i v e r a t s .  T h i s dose  of apomorphine a l s o decreased the percentage of r a t s d i s p l a y i n g penile r e f l e x e s , suggesting and  t h a t DA r e c e p t o r s  i n both t h e MPOA  lumbosacral s e c t i o n of t h e s p i n a l cord may i n t e g r a t e  r e f l e x e s and motor a s p e c t s of c o p u l a t i o n . (1990) r e p o r t e d  that  F i n a l l y , H u l l et a l .  i n f u s i o n of t h e D 2 - s e l e c t i v e  163502 (10 ug) t o the MPOA i n c r e a s e d  a g o n i s t LY  mount and i n t r o m i s s i o n  l a t e n c i e s and decreased t h e number of i n t r o m i s s i o n s sexually active rats.  The D l - s e l e c t i v e a g o n i s t  e f f e c t alone or together  penile  i n intact,  SKF-82526 had no  with LY 163502 on any aspect of  28 copulatory  behavior.  In contrast Cador,  to the r e s u l t s  and R o b b i n s  (1989)  to the nucleus  of  behavior.  were reduced f o l l o w i n g 10 u g .  However,  all  also  following  basolateral  amygdala  Although lesions effect rate  of  of  of  that  excitotoxic  of  responding  These d a t a  a m y g d a l a and n u c l e u s control  Taken t o g e t h e r , administration  of  responding  the r e s u l t s  DA a g o n i s t s  dthe  receptive  doses  that  for  a sexual  studies  suggest  that  that  female.  None  behavior  increased  lesioned  both the  the  stimulus  the conditioned  in both  of  in  reduced  a conditioned  of  the  stimulus.  In  increased  and shamstimulus  basolateral  accumbens p l a y an i m p o r t a n t  of c o n d i t i o n e d  of  significant  i n which the c o n d i t i o n e d  indicate  al.  a m y g d a l a had no  1 ug t o t h e accumbens  responding  during sessions  was o m i t t e d .  of  for  et  accumbens).  all  of  rats  bodies  however,  rate  control  Everitt  cell  3 or  3 ug d o s e  the copulatory  lesions;  instrumental  following  affected  w i t h amygdaloid  of  for  latencies  administration of  of  measures  to the  a sexually  rats  infusion  not  they s i g n i f i c a n t l y  responding  t h e doses of d-amphetamine  rates  several  ejaculated.  lesions  Everitt, infusion  t h e PEI and t h e  intraaccumbens  behavior,  instrumental  (1986),  bilateral  1 ug, but  increased rats  the presentation  bilateral  of  the basolateral  instrumental  addition,  that  ( w h i c h send p r o j e c t i o n s  on c o p u l a t o r y  signalled of  of  al.  accumbens a f f e c t e d  infusion  examined t h e e f f e c t  amphetamine  et  B o t h mount and i n t r o m i s s i o n  doses  reduced the p r o p o r t i o n  Hull  demonstrated  d-amphetamine copulatory  of  role  in  the  reward.  examining the both spinal  and  central  hypothalamic DA t e r m i n a l s facilitation  p l a y an important r o l e i n the  of c o p u l a t o r y  by DA a g o n i s t s .  r a t e , e j a c u l a t i o n , and p e n i l e r e f l e x e s  Although the a d m i n i s t r a t i o n  mesolimbic and m e s o s t r i a t a l DA t e r m i n a l s behavior s i g n i f i c a n t l y ,  of apomorphine t o  d i d not a l t e r  the a d m i n i s t r a t i o n  copulatory  of d-amphetamine t o  the nucleus accumbens decreased both mount and i n t r o m i s s i o n l a t e n c i e s and r e s t o r e d  the a b i l i t y of r a t s with amygdaloid  l e s i o n s t o perform i n s t r u m e n t a l reward.  responses f o r a secondary  These data suggest t h a t DA t r a n s m i s s i o n  sexual  indifferent  b r a i n areas may be important f o r d i f f e r e n t aspects of c o p u l a t o r y behavior. Effect  of DA  antagonists  Inferences can  about the normal r o l e of DA i n s e x u a l  be made by a s s e s s i n g  first  report  the e f f e c t s of DA a n t a g o n i s t s .  of an e f f e c t of a DA a n t a g o n i s t  was made by Zimbardo and Barry chlorpromazine  behavior  on s e x u a l  (1958), who observed  (1 mg/kg, IP) i n c r e a s e d  The behavior  that  mount and i n t r o m i s s i o n  l a t e n c i e s , decreased the e j a c u l a t i o n l a t e n c y , and decreased the number of i n t r o m i s s i o n s sexually active rats.  required  for ejaculation in intact,  Subsequent s t u d i e s have r e p o r t e d  e f f e c t s with a v a r i e t y of DA a n t a g o n i s t s . administration antagonists, and  the s y s t e m i c  of low-to-moderate doses of c e n t r a l l y - a c t i n g DA  such as the t y p i c a l n e u r o l e p t i c drugs h a l o p e r i d o l  pimozide, i n c r e a s e s  mount and i n t r o m i s s i o n l a t e n c i e s ,  decreases the number of i n t r o m i s s i o n s and,  similar  i n some cases,  required  for ejaculation,  decreases the e j a c u l a t i o n l a t e n c y and  increases  the PEI i n i n t a c t , s e x u a l l y a c t i v e r a t s  (Agmo&  Fernandez, 1989; A h l e n i u s & L a r s s o n , 1984a; Mcintosh & B a r f i e l d , 1984;  Pfaus & P h i l l i p s ,  1989).  t y p i c a l l y abolish copulatory neuroleptics, intromission  increase 1979).  such as c l o z a p i n e  once c o p u l a t o r y  behavior has been i n i t i a t e d  1989), whereas o t h e r s ,  (Ahlenius,  sexually  behavior  1989).  Pimozide b l o c k s  induced by e l e c t r i c  inactive rats  footshock  1987).  behavior  in intact,  (Antelman, Herndon, C a g g i u l a ,  induced by t h e D2 s e l e c t i v e a g o n i s t  latency  the s t i m u l a t i o n of  A dose of t h e D2 s e l e c t i v e a n t a g o n i s t  copulatory  such as the  but have no e f f e c t on t h e i n t r o m i s s i o n  mg/kg, SC) t h a t blocked the s u p r e s s i o n  (0.01  Heimann, & L a r s s o n ,  drug metoclopramide, decrease the number of  (Pfaus & P h i l l i p s , copulatory  (Pfaus  such as t h i o r i d a z i n e , a l s o  Other c e n t r a l l y - a c t i n g DA a n t a g o n i s t s ,  intromissions  al.,  Some a t y p i c a l  and s u l p i r i d e , i n c r e a s e  the e j a c u l a t i o n l a t e n c y  antiemetic  1975).  behavior.  l a t e n c i e s but have no e f f e c t on the number of  intromissions & Phillips,  Higher doses of these drugs  & Shaw,  r a c l o p r i d e (0.5  of the 22 kHz v o c a l i z a t i o n  quinpirole, i t s e l f  i n intact, sexually active rats  abolished  (Cagiano e t  A low dose of the DI s e l e c t i v e a n t a g o n i s t  SCH 23390  mg/kg, SC) had no e f f e c t on any measure of c o p u l a t o r y  behavior i n t h a t study.  The p e r i p h e r a l l y - a c t i n g DA  domperidone does not a f f e c t the c o p u l a t o r y  antagonist  behavior or p e n i l e  r e f l e x e s of i n t a c t , s e x u a l l y a c t i v e r a t s  ( F a l a s c h i e t a l . , 1981;  Pehek et a l . , 1988); however, i t e l e v a t e s  serum p r o l a c t i n l e v e l s  and  produces a s l i g h t  increase  i n the mount and i n t r o m i s s i o n  31 l a t e n c i e s of c a s t r a t e d , t e s t o s t e r o n e - t r e a t e d single administration spiperone  and  ( B a i l e y & Herbert,  1982).  Finally,  c l o z a p i n e decrease the number of mounts  intromissions/min  Unfortunately, For  and  or e s t r a d i o l  (Baum & S t a r r , 1980).  t h e r e are numerous i n c o n s i s t e n c i e s i n t h i s  example, low doses of h a l o p e r i d o l have been  reported  both to decrease  increase  (Ahlenius  (Ahlenius  & Larsson,  & Larsson,  1984a) and  1984b) the number of  Some i n v e s t i g a t o r s r e p o r t s u b s t a n t i a l i n c r e a s e s  intromissions.  i n the  f o l l o w i n g the a d m i n i s t r a t i o n of t y p i c a l n e u r o l e p t i c s Larsson,  both  i n c a s t r a t e d r a t s g i v e n s t e r o i d replacement  with d i h y d r o t e s t o s t e r o n e  literature.  male r a t s a f t e r a  1984a,b; Mcintosh & B a r f i e l d ,  PEI  (Ahlenius  1984), whereas others  &  find  no e f f e c t on t h i s measure at comparable doses of these drugs ( N a p o l i - F a r r i s et a l . , 1984; Phillips,  1989).  ejaculation  doses  (e.g.,  Smith, 1986;  study ( P a g l i e t t i  studies reported 0.1  et a l . , 1978;  A low dose of pimozide was  l a t e n c i e s i n one  whereas other  Paglietti  or 0.25  reported et a l . ,  doses  increase  1978)  e i t h e r no e f f e c t of comparably  Pfaus & P h i l l i p s ,  Clark  low &  1989), decreased  e j a c u l a t i o n l a t e n c i e s with moderate doses (e.g.,  with higher  to  mg/kg; Agmo & Fernandez, 1989;  Malmnas, 1973;  Mcintosh & B a r f i e l d ,  Pfaus &  1.0  mg/kg;  1984), or the e l i m i n a t i o n of e j a c u l a t i o n  (e.g.,  5.0  mg/kg; Pfaus & P h i l l i p s ,  1989).  The  a t y p i c a l n e u r o l e p t i c c l o z a p i n e does not a f f e c t the number of intromissions 1989)  i n i n t a c t , s e x u a l l y a c t i v e r a t s (Pfaus  & Phillips,  but decreases the mounting r a t e i n c a s t r a t e d r a t s  maintained on e i t h e r d i h y d r o t e s t o s t e r o n e  or e s t r a d i o l  (Baum &  32 Starr,  1980).  to receptors 1987).  As w i t h many DA a g o n i s t s , other  Moreover,  t h a n t h e DA s u b t y p e s substantial  m e t h o d o l o g y may c o n t r i b u t e Although systemic believed  to  centrally,  exert  few s t u d i e s  administered of  copulation.  latency to  first  of  Subsequently,  latencies infusion  factor.  Hull  et  t h e MPOA.  infusion  of  (1990)  the e f f e c t s  why SCH 23390  of  that  reported  increased of  These e f f e c t s  rats  intromissions  reduced III  to  the  the and  of  effect  the  Sachs'  on  other  activity. the  agonist  Dl-selective intromission following to  those  LY 1 6 3 5 0 2 .  SCH 23390  (3  I t -is d i f f i c u l t  following  the  initiated  identical  i n c r e a s e d mount and i n t r o m i s s i o n  r e d u c e d t h e number o f  that  form part  that  were  to  (20 and 40 ug)  intromissions  dose o f  o f LY 1 6 3 5 0 2 .  results  (1988c)  t h e mount and  the D2-selective  a behaviorally-inactive  potentiated  the  al.  or g e n e r a l motor  and d e c r e a s e d t h e number into  Pehek e t  cis-flupenthixol  measures  behavior  (10 ug)  centrally-  were a d m i n i s t e r e d  These d o s e s had l i t t l e  al.  of  and i n c r e a s e d b o t h t h e  ejaculation,  are  behavior  group r e p o r t e d  rats.  did,  findings.  DA a n t a g o n i s t s  cis-flupenthixol  ejaculations  SCH 23390  found a f t e r Moreover,  Hull's  reduced the p r o p o r t i o n  copulatory  antagonist  of  In those t h a t  copulatory rate aspects  of  have e x a m i n e d t h e e f f e c t s  infusions  number o f  experimental  on m a l e s e x u a l  sexually active  MPOA d r a m a t i c a l l y  in  inconsistent  i n w h i c h DA a n t a g o n i s t s  intact,  observed t h a t  total  effects  DA a n t a g o n i s t s .  two s t u d i e s  MPOA o f  t o these  bind  (Tamminga & G e r l a c h ,  differences  administration  their  many DA a n t a g o n i s t s  ug) to  latencies infusion  to  explain and the  MPOA but c i s - f l u p e n t h i x o l r e c e p t o r s ) d i d not. of DI r e c e p t o r s  (which binds  At f i r s t  glance,  t o both DI and D2 i t would seem t h a t blockade  i n the MPOA i s r e s p o n s i b l e f o r the major  of s y s t e m i c a l l y a d m i n i s t e r e d  DA a n t a g o n i s t s .  suggest t h a t the D2/D1 r a t i o  i n the MPOA i s an important  i n t h e r e g u l a t i o n of male s e x u a l behavior  effects  However, these  data  factor  because t h e s e l e c t i v e  s t i m u l a t i o n of D2 r e c e p t o r s or the s e l e c t i v e blockade of DI receptors  i n t h a t area produces i d e n t i c a l e f f e c t s : a d e l a y  i n the  i n i t i a t i o n of c o p u l a t i o n and a r e d u c t i o n i n the e j a c u l a t o r y threshold.  Although DA r e c e p t o r s  important  role  behavior,  a r o l e of DA r e c e p t o r s  r u l e d out. the e f f e c t spinal  i n the MPOA o b v i o u s l y p l a y an  i n the i n i t i a t i o n and r a t e of male  i n other b r a i n areas  No s t u d i e s have y e t been p u b l i s h e d of DA a n t a g o n i s t s  copulatory cannot be  t h a t have examined  i n other b r a i n r e g i o n s  or i n the  cord.  In summary, the r e s u l t s of s t u d i e s u s i n g DA a n t a g o n i s t s i n d i c a t e t h a t decreases i n c e n t r a l DA a c t i v i t y d e l a y or a b o l i s h the  initiation  of c o p u l a t i o n i n s e x u a l l y a c t i v e male r a t s .  In  r a t s t h a t i n i t i a t e c o p u l a t i o n , these drugs d i s r u p t measures of c o p u l a t o r y r a t e and h i t r a t e by d e c r e a s i n g intromissions before ejaculations. role  both the number of  e j a c u l a t i o n and the t o t a l number of  DA r e c e p t o r s  i n t h e MPOA may p l a y an  i n the d i s r u p t i o n of male s e x u a l  behavior  important  induced  by these  drugs. Lesions  of DA pathways  Another way t o i n f e r the normal f u n c t i o n i n g of b r a i n DA  34 systems i n male s e x u a l behavior  i s t o d e s t r o y DA c e l l  p r o j e c t i o n f i b e r s , or t e r m i n a l r e g i o n s . either  electrolytically,  by p a s s i n g s u f f i c i e n t  electrode t o destroy surrounding infusing a neurotoxin  T h i s can be  bodies, accomplished  c u r r e n t through an  t i s s u e , or n e u r o c h e m i c a l l y , by  such as 6-hydroxydopamine  s e l e c t i v e l y d e s t r o y s catecholamine  (6-OHDA) which  neurons i n the b r a i n .  Some  s t u d i e s a l s o examine the a b i l i t y of DA a g o n i s t s or a n t a g o n i s t s t o a f f e c t male s e x u a l behavior or t e r m i n a l s .  Although  f o l l o w i n g l e s i o n s of DA c e l l  c o p u l a t o r y behavior  bodies  has been assessed i n  male r a t s f o l l o w i n g l e s i o n s of s e v e r a l b r a i n areas t h a t c o n t a i n DA r e c e p t o r s or f i b e r s , o n l y t h r e e systems have been s t u d i e d i n some d e t a i l : the i n c e r t o h y p o t h a l a m i c  (with DA t e r m i n a l s i n the  MPOA), the m e s o s t r i a t a l (with DA t e r m i n a l s i n the d o r s a l s t r i a t u m ) , and the m e s o l i m b i c / m e s o c o r t i c a l interest  i n the nucleus  accumbens,  (with DA t e r m i n a l s of  amygdala, and o l f a c t o r y  tubercle). The e f f e c t  of a g e n e r a l d e p l e t i o n of b r a i n catecholamines  the c o p u l a t o r y behavior  of i n t a c t , s e x u a l l y a c t i v e male r a t s was  i n v e s t i g a t e d by C a g g i u l a , Shaw, Antelman, and Edwards t h a t study,  6-OHDA was i n f u s e d i n t o the l a t e r a l  (1976).  ( t o i n c r e a s e the amount of catecholamine  D e s p i t e the f a c t t h a t the combination  In  ventricles  f o l l o w i n g p e r i p h e r a l i n j e c t i o n of t h e monoamine oxidase pargyline  on  inhibitor  depletion).  of 6-OHDA and p a r g y l i n e  produced a 74% d e p l e t i o n of caudate DA, and 81% and 54% d e p l e t i o n s of c o r t i c a l and hypothalamic n o r e p i n e p h r i n e , treatment  this  produced o n l y a t r a n s i e n t r e d u c t i o n i n the t o t a l  number  of  ejaculations,  i n c o n t r a s t to r a t s t r e a t e d with  p a r g y l i n e alone or the v e h i c l e . week a f t e r  treatment  T h i s e f f e c t was  but had d i s a p p e a r e d  either observed  by the second  However, subsequent a d m i n i s t r a t i o n of the t y r o s i n e i n h i b i t o r alpha-methyl-p_-tyrosine affect  the c o p u l a t o r y behavior  intromission  latencies,  Ills,  (AMPT), a t a dose t h a t d i d not  PEIs, reduced  i n t r o m i s s i o n s , and d r a m a t i c a l l y reduced t h a t a c h i e v e d an e j a c u l a t i o n . did  not  intact).  of r a t s  I n t e r e s t i n g l y , some of these  Furthermore,  only half  p a r g y l i n e c o p u l a t e d with females  haloperidol  tails  of the r a t s  treated  latencies,  i n c r e a s e d mount and  Ills,  i n t r o m i s s i o n l a t e n c i e s with but almost  Thus, l a r g e catecholamine  a  reduced  h y p e r s e n s i t i v e to treatments they reduce cues.  the copulatory  d e p l e t i o n s have  of male r a t s  r e l a t i v e l y normal c o n d i t i o n s , but they render  some e x t e r n a l s e x u a l  and  a l l initiated  e f f e c t on the c o p u l a t o r y behavior  s y n t h e s i s and  the  Some n o n l e s i o n e d r a t s a l s o d i s p l a y e d  " h a l o p e r i d o l i z e d " females, behavior with them.  lordosis  d i s p l a y e d i n c r e a s e d mount and  i n c r e a s e d PEIs and  number of e j a c u l a t i o n s .  given  with  L e s i o n e d r a t s t h a t d i d i n i t i a t e c o p u l a t i o n with  intromission  rats  were  (which b l o c k s p r o c e p t i v e behavior but l e a v e s  " h a l o p e r i d o l i z e d " females  little  the percentage  that t y p i c a l l y stimulates copulation in  sexually inactive rats. 6-OHDA and  i n c r e a s e d the  the number of  i n i t i a t e c o p u l a t o r y behavior unless t h e i r  p i n c h e d , a procedure  week.  hydroxylase  of n o n l e s i o n e d r a t s , and  one  t h a t decrease  under  those males  catecholamine  the males* b e h a v i o r a l r e s p o n s i v e n e s s  to  Electrolytic disrupt  1966/67;  a l s o be p r o d u c e d neurotoxin  that  1968;  castrated  handling,  1983) .  of  into  insensitive intact,  presentation  full  or  1982).  This suggests  observed a f t e r  behavior,  D2-S1 r e c e p t o r of  Although the  can  a al.,  b e c a u s e t h e MPOA in the  brain  of  copulation  in  R a t s w i t h MPOA  that  can  stimulate  inactive  tail  pinch,  & Larsson, treating agonist  copulatory  rats or  (e.g., flank  1966/67;  Meisel,  MPOA-lesioned  lisuride  behavior  in copulatory  rats  activates  (Hansen e t  decreased monoaminergic  to the d i s r u p t i o n  tone  in  al., the  behavior  MPOA l e s i o n s . to the a b i l i t y  unilateral  infusions  to affect  sexually active  female,  effect  (Hansen e t  neurons  1967).  (Heimer &  acid,  and i m p l a n t a t i o n  1 9 6 8 ; Heimer  t h e MPOA t o d i s r u p t  reported not  bodies  t h e MPOA f a c i l i t a t e s  a novel  that  This  ibotenic  important  1966; L i s k ,  of  patterns  In contrast of  cell  as n o t e d p r e v i o u s l y ,  partial  MPOA c o n t r i b u t e s  of  t o many p r o c e d u r e s  & Sachs,  However,  1973)  t h e MPOA s e v e r e l y  o f male r a t s  s e x u a l l y exhausted or  w i t h the nonselective  lesions  destroys  of  1979).  steroid-concentrating  (Davidson,  Barfield  infusion  are e s p e c i a l l y  directly  in  behavior  & van D i s ,  the  Sar & S t u m p f ,  rats  are  copulation  shock;  following selectively  site  testosterone  lesions  the caudal part  Van de P o l l  These r e s u l t s  i s a major (Pfaff,  of  or a b o l i s h t h e c o p u l a t o r y  Larsson,  1982) .  lesions  rats  of  electrolytic  or a b o l i s h male of  6-OHDA i n t o  the copulatory  (Bitran,  Hull,  behavior  Holmes,  6-OHDA r e g i m e n used i n t h a t  or  ibotenic  acid  copulatory t h e MPOA w e r e of  intact,  & Lookingland,  study resulted  1988).  in a  37 s m a l l but s i g n i f i c a n t decrease i n DA c o n c e n t r a t i o n of t h e DA m e t a b o l i t e differ  dihydroxyphenylacetic  (23%),  levels  a c i d (DOPAC) d i d not  s i g n i f i c a n t l y among 6-OHDA-treated r a t s and c o n t r o l s ,  suggesting  t h a t impulse flow had not changed i n the 6-OHDA-  treated rats.  However,  c o p u l a t o r y behavior  a dose of AMPT t h a t d i d not a f f e c t the  of n o n l e s i o n e d  r a t s , decreased  the t o t a l  number of e j a c u l a t i o n s and i n c r e a s e d both the e j a c u l a t i o n l a t e n c i e s and PEIs of 6-OHDA-treated r a t s a f t e r MPOA, s u g g e s t i n g  t h a t these  d i s r u p t i o n produced by AMPT. infused  i n f u s i o n i n t o the  r a t s were more s e n s i t i v e t o t h e S i m i l a r l y , a dose of apomorphine  i n t o the MPOA t h a t had no e f f e c t on t h e t o t a l number of  ejaculations  i n nonlesioned  i n 6-OHDA-treated r a t s .  r a t s (0.2 ug) i n c r e a s e d t h i s number  Finally,  t h e d i s r u p t i v e e f f e c t s of a low  dose of apomorphine i n f u s e d i n t o t h e MPOA of n o n l e s i o n e d (e.g.,  rats  i n c r e a s e d e j a c u l a t i o n l a t e n c y , PEI, I I I , and decreased  number of e j a c u l a t i o n s ) were a b o l i s h e d treatment, s u g g e s t i n g  t h a t these  e f f e c t s were due i n n o n l e s i o n e d  r a t s t o t h e s t i m u l a t i o n of p r e s y n a p t i c Together, these  f o l l o w i n g 6-OHDA  DA a u t o r e c e p t o r s .  r e s u l t s suggest t h a t r a t s with  6-OHDA l e s i o n s of  the MPOA are h y p e r s e n s i t i v e both t o treatments t h a t decrease catecholamine s y n t h e s i s and t o a g o n i s t a c t i v a t i o n of p o s t s y n a p t i c DA r e c e p t o r s . Electrolytic  l e s i o n s of t h e A9 c e l l  n i g r a pars compacta  bodies  i n the substantia  (which p r o j e c t DA f i b e r s mainly t o the d o r s a l  s t r i a t u m ) d i s r u p t s e v e r a l measures of male c o p u l a t o r y Bilateral  l e s i o n s have been r e p o r t e d  behavior.  t o i n c r e a s e mount l a t e n c i e s ,  38 decrease the number of mounts/min, and decrease the number of ejaculations i n intact, sexually active rats Edwards, 1986), but not t o a f f e c t other behavior.  These l e s i o n s d e p l e t e d  Iuvone, &  measures of c o p u l a t o r y  DA l e v e l s i n the caudate by an  average of 56%. In c o n t r a s t , u n i l a t e r a l have been r e p o r t e d  (Brackett,  l e s i o n s of the compacta  t o i n c r e a s e mount and i n t r o m i s s i o n l a t e n c i e s ,  decrease the number of i n t r o m i s s i o n s , and i n c r e a s e postejaculatory v o c a l i z a t i o n duration sexually active rats  both the  and the PEI i n i n t a c t ,  (Mcintosh & B a r f i e l d ,  1984).  Although  these  e f f e c t s were i d e n t i c a l t o those produced by pimozide i n t h a t study, u n i l a t e r a l but  significant,  i n f u s i o n s of 6-OHDA produced a o n l y a s m a l l , increase  i n the PEI.  Bilateral  of the d o r s a l s t r i a t u m a l s o i n c r e a s e d Cador, T a y l o r  & Everitt,  access t o r e c e p t i v e  proceptive  mesostriatal  significantly  access t o r e c e p t i v e  electrolytic  a f f e c t other  i f t h e males i n  females t r e a t e d  with  eliminates  (VTA)  that  behavior.  l e s i o n s of the A10 c e l l increased  in i n t a c t , sexually active rats not  behavior.  i n both a r o u s a l and  performance a s p e c t s of male c o p u l a t o r y  v e n t r a l tegmental area  given  The r e s u l t s of these s t u d i e s suggest  DA systems a r e i n v o l v e d  Bilateral  proceptive  - f l u p e n t h i x o l , a treatment t h a t  behaviors.  (Robbins,  i f t h e males were  females t h a t d i s p l a y e d  t h a t study were g i v e n the DA a n t a g o n i s t  mount l a t e n c i e s  1989), but o n l y  Mount l a t e n c i e s were not e l e v a t e d  6-OHDA l e s i o n s  mount l a t e n c i e s and PEIs  (Brackett  measures of c o p u l a t o r y  bodies i n the  e t a l . , 1986), but d i d  behavior.  Those l e s i o n s  produced an average 77% d e p l e t i o n of DA i n the nucleus accumbens.  39 Similarly, bilateral important t e r m i n a l increased  6-OHDA l e s i o n s of the nucleus accumbens,  region  of the A10  projections,  mount l a t e n c i e s (Robbins et a l . , 1989).  corticomedial projections,  amygdala, another t e r m i n a l increased  the number of  the e j a c u l a t i o n l a t e n c y , and to s e x u a l  region  Lesions  of  of the A10  DA  i n t r o m i s s i o n s , the  decreased the number of  H a r r i s & Sachs, 1975).  these e f f e c t s were r e p r o d u c i b l e primed with e s t r o g e n alone, incidence  of p r o c e p t i v e  only  behaviors  normal c o p u l a t o r y  primed with e s t r o g e n and  and  (Giantonio,  However, some of  i f the s t i m u l u s  females were the  (Perkins, Perkins,  & Hitt,  amygdala l e s i o n s d i s p l a y e d  behavior  i n t h a t study w i t h  progesterone.  no  females  As noted above, E v e r i t t  et a l . (1989) demonstrated t h a t b i l a t e r a l the b a s o l a t e r a l amygdala had  III,  the  ejaculations  a treatment t h a t reduces  Rats with c o r t i c o m e d i a l  apparently  of  also  exhaustion in i n t a c t , s e x u a l l y a c t i v e r a t s  Lund, & G e r a l l , 1970;  1980).  DA  an  e x c i t o t o x i c l e s i o n s of  e f f e c t on the c o p u l a t o r y  behavior  i n t a c t , s e x u a l l y a c t i v e r a t s ; however, these l e s i o n s reduced  the r a t e of operant r e s p o n d i n g f o r a secondary s e x u a l Finally, region  l e s i o n s of the  of the A10  DA  behavior of male r a t s Taken t o g e t h e r , mesocortical, complicated  o l f a c t o r y t u b e r c l e , another  p r o j e c t i o n s , had (Perkins  no  terminal  e f f e c t on the  copulatory  et a l , 1980).  these r e s u l t s suggest t h a t the  n i g r o s t r i a t a l , and  diencephalic  DA  r o l e i n the c o n t r o l of both a r o u s a l  a s p e c t s of male c o p u l a t o r y  reward.  behavior.  mesolimbic,  systems p l a y a and  performance  I t i s i n t e r e s t i n g to note  t h a t l e s i o n s of the d o r s o l a t e r a l tegmentum a b o l i s h  copulatory  behavior al.,  i n a manner s i m i l a r  1986).  to  The MPOA p r o j e c t s  lesions efferent  f o r e b r a i n bundle to the d o r s o l a t e r a l b o t h t h e A9 and A10 c e l l amygdala p r o j e c t s to disentangle  effect  of  electrolytic  efferent  of  6-OHDA i s lesions  Ex v i v o  analyses  of  liquid for  of  substances  h a v e been p u b l i s h e d following  periods  of  (HPLC)  of  copulatory  behavior  locomotion,  or  Carlsson,  accumbens,  one e j a c u l a t i o n )  relatively  but  brain  of  or  in  unspecified  pressure a new  three  DA  intact,  and  Larsson  neostriatum, following  sexual a c t i v i t y 25 m i n o f  (at  least  treadmill  activity  i n t h e n e o s t r i a t u m and anterior  studies  sexually  Hjorth,  Sexual  tool  activity  hypothalamus  female,  i n t h e septum or  of  regions  To d a t e ,  DOPA i n t h e  10 m i n i n t h e home c a g e .  not  lack  effects  with high  Hillegaart,  and a n t e r i o r  with a receptive  i n c r e a s e d DOPA a c c u m u l a t i o n accumbens,  large  have examined r e g i o n a l  examined t h e a c c u m u l a t i o n of  10 m i n o f  the  the general  investigators  behavior.  (1987)  either  of  detection  in various  rats.  nucleus  difficult  produced by s y s t e m i c  have g i v e n  active  septum,  is  in light  metabolites  activity  periods  Ahlenius,  corticomedial  metabolites  and t h e i r  that  to  DA a n t a g o n i s t s .  assessing t r a n s m i t t e r controlled  et  medial  in addition  It  Furthermore,  in the electrochemical  chromatography  following  the  puzzling given both the  DA and  Recent advances  through the  tegmentum,  lesion studies  and t h e e f f e c t s  administration  fibers  t o t h e MPOA.  these systems.  central  transmitter  of  t h e MPOA ( B r a c k e t t  Moreover,  fibers  the r e s u l t s  interconnection of  groups.  of  nucleus  hypothalamus,  in  comparison with c o n t r o l r a t s l e f t  i n the home cage.  locomotion i n c r e a s e d DOPA accumulation not i n the other t h r e e r e g i o n s . catecholamine  Treadmill  i n the n e o s t r i a t u m , but  These r e s u l t s suggest  s y n t h e s i s (as determined  by DOPA  accumulation)  i n c r e a s e s i n the nucleus accumbens as a s p e c i f i c  f u n c t i o n of  s e x u a l a c t i v i t y and i n the n e o s t r i a t u m as a n o n s p e c i f i c of e i t h e r s e x u a l a c t i v i t y or t r e a d m i l l  that  locomotion.  function  Although  s u g g e s t i v e , these r e s u l t s do not s p e c i f y e x a c t l y what a s p e c t s of c o p u l a t o r y a c t i v i t y c o n t r i b u t e d to the i n c r e a s e d DOPA accumulation  i n e i t h e r the nucleus accumbens or n e o s t r i a t u m .  Moreover, these r e s u l t s do not i n d i c a t e whether the i n c r e a s e d DOPA accumulation  l e a d s t o i n c r e a s e d DA r e l e a s e or u t i l i z a t i o n ,  because l e v e l s of DA or i t s m e t a b o l i t e d i h y d r o x y p h e n y l a c e t i c a c i d (DOPAC) l e v e l s were not e v a l u a t e d . L e v e l s of DA and DOPAC i n the p a r i e t a l c o r t e x , p r e o p t i c r e g i o n , mediobasal  hypothalamus, and lumbosacral s p i n a l c o r d have  been examined i n r a t s t h a t achieved e i t h e r  one e j a c u l a t i o n or  i n t r o m i s s i o n s but no e j a c u l a t i o n , compared t o s e x u a l l y  inactive  r a t s t h a t d i d not i n i t i a t e c o p u l a t o r y behavior with r e c e p t i v e females  (Mas, d e l C a s t i l l o ,  Guerra, Davidson,  & B a t t a n e r , 1987).  In t h a t study, both DA and DOPAC l e v e l s were s i g n i f i c a n t l y elevated  i n the p r e o p t i c region a f t e r e j a c u l a t i o n .  Although  both  DA and DOPAC l e v e l s were e l e v a t e d i n the p r e o p t i c r e g i o n a f t e r i n t r o m i s s i o n alone, o n l y the DOPAC e l e v a t i o n reached significance.  DA l e v e l s  statistical  i n the lumbosacral c o r d were a l s o  elevated s i g n i f i c a n t l y after  i n t r o m i s s i o n a l o n e , but not a f t e r  42 e j a c u l a t i o n , suggesting cord may c o n t r i b u t e reflexes during  t h a t DA mechanisms i n t h i s r e g i o n  t o t h e descending i n h i b i t i o n of e j a c u l a t o r y  intromission.  cord were u n d e t e c t a b l e , evaluated.  Unfortunately,  DOPAC l e v e l s i n the  thus DA u t i l i z a t i o n c o u l d  not be  Changes i n DA or DOPAC l e v e l s d i d not occur i n e i t h e r  the p a r i e t a l c o r t e x  or mediobasal hypothalamus.  suggest t h a t DA r e l e a s e and u t i l i z a t i o n increased  of the  f o l l o w i n g an e j a c u l a t i o n .  These r e s u l t s  i n the p r e o p t i c r e g i o n i s  Intromission  DA u t i l i z a t i o n but not n e c e s s a r i l y DA r e l e a s e  alone  increases  i n the p r e o p t i c  region. F i n a l l y , a s t u d y by Hoffman, G e r a l l , and K a l i v a s examined DA and DOPAC l e v e l s i n the MPOA, a r c u a t e  (1987)  nucleus/median  eminence, or medial f o r e b r a i n bundle of i n t a c t , s e x u a l l y a c t i v e r a t s t h a t had e i t h e r c o p u l a t e d  to sexual  e x h a u s t i o n or were run  i n a m o t o r - d r i v e n wheel, compared t o i n t a c t , s e x u a l l y i n a c t i v e control rats.  Each r a t i n t h e wheel-running c o n d i t i o n was yoked  to a r a t i n t h e s e x u a l  e x h a u s t i o n c o n d i t i o n such t h a t t h e wheel  s t a r t e d r o t a t i n g when mounts were i n i t i a t e d after  ejaculation.  and stopped r o t a t i n g  DA l e v e l s i n t h e MPOA, but not i n the arcuate  nucleus or medial f o r e b r a i n bundle, were e l e v a t e d i n both s e x u a l l y exhausted and a c t i v e r a t s . differences  i n DOPAC c o n c e n t r a t i o n  the t h r e e b r a i n r e g i o n s ,  significantly  Although no  were d e t e c t e d  t h e r e was a s i g n i f i c a n t  among groups i n negative  c o r r e l a t i o n between t h e number of e j a c u l a t i o n s and DOPAC concentration DA u t i l i z a t i o n  i n t h e medial f o r e b r a i n bundle.  T h i s suggests t h a t  i n t h i s r e g i o n was i n v e r s e l y r e l a t e d t o the number  of e j a c u l a t i o n s . together  with  The i n c r e a s e d  DA c o n c e n t r a t i o n  i n t h e MPOA,  t h e l a c k of change i n DOPAC c o n c e n t r a t i o n ,  that DA u t i l i z a t i o n and/or r e l e a s e was attenuated  suggests  i n the MPOA  f o l l o w i n g l e n g t h l y bouts of locomotor a c t i v i t y , t h e m a n i p u l a t i o n common t o both the s e x u a l Taken t o g e t h e r ,  exhaustion  and f o r c e d a c t i v i t y  groups.  these r e s u l t s i n d i c a t e t h a t DA s y n t h e s i s ,  r e l e a s e , and/or u t i l i z a t i o n may i n c r e a s e d u r i n g c o p u l a t i o n i n s e v e r a l DA t e r m i n a l r e g i o n s , n o t a b l y neostriatum, controlled neostriatum An  and MPOA.  t h e nucleus accumbens,  However, i n the two s t u d i e s  that  f o r locomotor a c t i v i t y , t h e e f f e c t s observed and MPOA were not s p e c i f i c t o c o p u l a t o r y  a n a l y s i s of DA r e l e a s e with  help r e s o l v e t h e q u e s t i o n  i n the  behavior.  f i n e r temporal r e s o l u t i o n would  of b e h a v i o r a l  specificity.  Problems of i n t e r p r e t a t i o n T h i s review of t h e l i t e r a t u r e does not lend simple  explanation  c e r t a i n cases,  of t h e r o l e of DA i n male s e x u a l  DA a g o n i s t s  r a t e of c o p u l a t i o n  facilitate  to a  behavior.  In  e j a c u l a t i o n or i n c r e a s e t h e  i n s e x u a l l y a c t i v e r a t s and f a c i l i t a t e t h e  i n i t i a t i o n of c o p u l a t i o n antagonists  itself  i n sexually inactive rats.  can d i s r u p t the i n i t i a t i o n of c o p u l a t i o n  a c t i v e r a t s , they a l s o f a c i l i t a t e c o p u l a t i o n has been i n i t i a t e d . l e s i o n s of DA t e r m i n a l s  Although DA i n sexually  e j a c u l a t i o n i n those r a t s once  Under c e r t a i n  circumstances,  produce e f f e c t s s i m i l a r t o t h e  a d m i n i s t r a t i o n of DA a n t a g o n i s t s . these f i n d i n g s , ex v i v o a n a l y s e s  In g e n e r a l  agreement  with  of DA s y n t h e s i s , r e l e a s e , and  u t i l i z a t i o n r e v e a l t h a t DA a c t i v i t y  i s increased  i n mesolimbic,  nigrostriatal,  and d i e n c e p h a l i c DA t e r m i n a l r e g i o n s f o l l o w i n g  d i f f e r e n t k i n d s of c o p u l a t o r y e x p e r i e n c e .  Although  inferences  can be made about the r o l e of DA i n male s e x u a l behavior these approaches, none p r o v i d e s an adequate account systems do d u r i n g male s e x u a l b e h a v i o r .  of what DA  Moreover, t h e r e a r e  numerous i n c o n s i s t e n c i e s t h a t are d i f f i c u l t t o r e s o l v e . i n c o n s i s t e n c i e s may r e s u l t  from a combination  methodological  i n c l u d i n g the use of animals  procedures,  based on  These  of d i f f e r e n t with  d i f f e r e n t b a s e l i n e s of s e x u a l b e h a v i o r , d i f f e r e n t r o u t e s of drug a d m i n i s t r a t i o n , d i f f e r e n t time c o u r s e s , d i f f e r e n t methods of t e s t i n g s e x u a l b e h a v i o r , d i f f e r e n t types of t e s t i n g chambers, and the use of s t a t i s t i c a l Relatively l i t t l e  procedures  t h a t v a r y i n power.  attempt has been made to c r i t i c a l l y  e v a l u a t e the r o l e of DA i n s e x u a l m o t i v a t i o n .  I t cannot be  assumed, f o r example, t h a t DA a g o n i s t s s t i m u l a t e c o p u l a t i o n i n s e x u a l l y i n a c t i v e r a t s and f a c i l i t a t e a c t i v e r a t s by a common mechanism. a s c r i b e a simple behavior  i n sexually  I t i s also d i f f i c u l t to  i n c e n t i v e r o l e t o DA systems i n the s e x u a l  of male r a t s .  These systems appear to r e g u l a t e many  a s p e c t s of s e x u a l b e h a v i o r , the f e e d i n g or avoidance  including penile reflexes.  literatures,  suspect t h a t t h e i n i t i a t i o n to  ejaculation  Unlike  t h e r e i s no reason to  of c o p u l a t i o n i s any more s e n s i t i v e  the d i s r u p t i o n of DA systems than other a s p e c t s of c o p u l a t i o n .  Without a c l e a r d i s t i n c t i o n between a n t i c i p a t o r y and consummatory a s p e c t s of c o p u l a t o r y b e h a v i o r , from the present  i t i s i m p o s s i b l e to determine  l i t e r a t u r e what r o l e DA p l a y s i n i n c e n t i v e  45 sexual  motivation.  L e v e l Changing: A New Recently, behavior  was  a new  Measure of A n t i c i p a t o r y Sexual Behavior  form of s e x u a l l y motivated a n t i c i p a t o r y  c h a r a c t e r i z e d f o r male r a t s i n the b i l e v e l  designed by Mendelson and is depicted  in Figure  Gorzalka  2 (Panel A,  (1987). filled  chambers  T h i s behavior,  c i r c l e s , squares,  t r i a n g l e s ) , appeared as high r a t e s of l e v e l changing d u r i n g 5-min a d a p t a t i o n  periods  p r i o r to the  Pfaus, Mendelson, & P h i l l i p s ,  5-min a d a p t a t i o n T h i s behavior  was  periods  1988).  This  attenuated  female was  discontinued  castration  (Panel C ) .  increased  females or other  (Panel A,  increased  open squares and  B, c l o s e d c i r c l e s ) or  following  be maintained by the  of e i t h e r a s e x u a l l y r e c e p t i v e or n o n r e c e p t i v e  previous For  a n a l y s i s of l e v e l changing has methods used to assess  of of a  level  presentation  female.  s e v e r a l advantages over  a n t i c i p a t o r y sexual  example, i n c o n t r a s t to analyses  the  of a  T h i s i n d i c a t e s t h a t the a c q u i s i t i o n  they can  to  triangles).  s e x u a l l y r e c e p t i v e female; however, once s t a b l e r a t e s of  The  access  r a t e s of l e v e l changing r e q u i r e s the p r e s e n t a t i o n  changing are a c q u i r e d ,  level  males f o l l o w i n g  when the p r e s e n t a t i o n  (Panel  the  (Mendelson & Pfaus,  changing d i d not develop i n s e x u a l l y a c t i v e males g i v e n either s e x u a l l y nonreceptive  and  i n t r o d u c t i o n of a s e x u a l l y  r e c e p t i v e female r a t f o r a t e s t of c o p u l a t i o n 1989;  which  of running  motivation.  speed  in straight  a l l e y s or T-mazes, the e v a l u a t i o n of l e v e l changing i s u n l i k e l y to be hindered  by c e i l i n g  effects.  Baseline  r a t e s of  level  46  F i g u r e 2.  L e v e l changes d i s p l a y e d by s e x u a l l y a c t i v e males i n the b i l e v e l chambers designed by Mendelson and G o r z a l k a (1987). A: A c q u i s i t i o n ; Group R was g i v e n access to s e x u a l l y r e c e p t i v e females on each t e s t ; Group N was g i v e n access to s e x u a l l y n o n r e c e p t i v e females on t e s t s 1 through 8, a f t e r which they were g i v e n access to s e x u a l l y r e c e p t i v e females; and Group M was g i v e n access t o other males on t e s t s 1 through 8, a f t e r which they were g i v e n access to s e x u a l l y r e c e p t i v e females. B: E x t i n c t i o n ; Group N was g i v e n access t o s e x u a l l y n o n r e c e p t i v e females on each t e s t ; and Group 0 d i d not r e c e i v e access to any c o n s p e c i f i c f o l l o w i n g the 5-min h a b i t u a t i o n p e r i o d s . C: E f f e c t of c a s t r a t i o n . Values are means + SE. From Pfaus, Mendelson, and P h i l l i p s (1988).  O  09  MEAN NUMBER OF LEVEL CHANGES o I  ••» i  *  1  •  i  a  L  MEAN NUMBER OF LEVEL CHANGES 8  j  o i  M  i  »•  1  •  1  »  1  MEAN NUMBER OF LEVEL CHANGES S I  o  M  I  1  > •  • • • r111  * * 3  *. I  o> 1  « 1  5 1  48 changing  are  observed  at  less for  time  female level  one  to  than  or  level  movements  by  in  wild.  to  the  than  antagonist simple,  measures of  DA  of  male search  less  effects  measures  to  and  can  be  females.  In  of  more  of  castration,  objective used  in  by  low  changing of  behavior  bar  grids  reach  male  rats  that  to  by in  level latencies  sensitive  the  DA  receptor  represent  anticipatory with  bar  l e v e l - t o -  more  may  with  description  by  of  be  press  to  the  the  was  doses  measure  or  comparison  of  i t  can  changing  intromission  conjunction  sexual  mazes  females  or  rats  level  demonstrated  mount  level  of  natural:  estrous  than  of  e l e c t r i f i e d  reminiscent  for  Thus  consummatory  a sexual  traditional  evaluate  the  effects  antagonists.  Overview The  experiments  integrated that  run  disruption  haloperidol.  that  to  experiments  sensitive  number  analysis  rats  crossing  preliminary  sensitive,  motivation  the  the  disruptive  those  training  receptive  large  the  are  burrows  was  makes  the  of  Although  a  appears  (1962) the  and  changing  Calhoun  changing  This  sexually  behavior  rats,  rapidly  time.  consuming  access  pressing  acquired  approach  incorporates  analyses aspects stable  of of  DA  baselines  the  reported to  both  function  sexual  of  the  in  study  this of  Experiments thesis  DA  pharmacological during  behavior. of  Present  level  both  The  male  and  sexual  of  and  rats  an behavior  electrochemical  anticipatory  use  changing  in  represent  with  copulatory  and  consummatory  r e l a t i v e l y behavior  in  the  49 present experiments  a l s o a l l o w s more meaningful  comparisons of  drug e f f e c t s and e l e c t r o c h e m i c a l p r o f i l e s . Experiment  I i n v e s t i g a t e d the s t a t i s t i c a l  r e l a t i o n among the  measures of a n t i c i p a t o r y and consummatory s e x u a l d i s p l a y e d by male r a t s i n the b i l e v e l chamber.  behavior Accordingly,  m u l t i p l e c o r r e l a t i o n s among these measures were c a l c u l a t e d and subjected to factor a n a l y s i s using orthogonal r o t a t i o n s . approach generated account  This  the minimum number of f a c t o r s n e c e s s a r y t o  f o r the v a r i a n c e among the measures, and thus p r o v i d e d a  t h e o r e t i c a l b a s i s f o r understanding s e x u a l behavior  the' deep s t r u c t u r e of male  i n the b i l e v e l chambers.  The r e s u l t s of t h i s  a n a l y s i s were compared to the r e s u l t s of a p r e v i o u s a n a l y s i s study conducted Experiment  by Sachs  factor  (1978).  II examined the dose-response  e f f e c t s of s y s t e m i c  a d m i n i s t r a t i o n of DA a n t a g o n i s t s on a n t i c i p a t o r y and consummatory a s p e c t s of male s e x u a l b e h a v i o r .  T h i s study extended  previous  f i n d i n g s t h a t t y p i c a l and a t y p i c a l n e u r o l e p t i c s a f f e c t behavior of male r a t s d i f f e r e n t l y  (Pfaus & P h i l l i p s ,  the s e x u a l  1989), and  p r o v i d e d a p r e l i m i n a r y assessment of the r o l e s of DI and D2 r e c e p t o r s i n male s e x u a l In Experiment  behavior.  I I I , the dose-response  e f f e c t s of c e n t r a l  a d m i n i s t r a t i o n of the DA r e c e p t o r a n t a g o n i s t h a l o p e r i d o l i n t o the nucleus accumbens, n e o s t r i a t u m , and MPOA were examined d u r i n g a n t i c i p a t o r y and consummatory a s p e c t s of male s e x u a l  behavior.  The r e s u l t s of t h i s study i n d i c a t e t h a t mesolimbic, m e s o s t r i a t a l , and  i n c e r t o h y p o t h a l a m i c DA systems c o n t r o l d i f f e r e n t aspects of  50 s e x u a l behavior Finally,  i n the male r a t .  i n Experiment  examine DA e f f l u x catecholamine  IV, i n v i v o voltammetry was used to  i n the nucleus accumbens and s t r i a t u m , and  efflux  i n the MPOA, of i n t a c t , s e x u a l l y a c t i v e  rats  d u r i n g a n t i c i p a t o r y and consummatory a s p e c t s of s e x u a l b e h a v i o r . D i r e c t comparisons  of the s e x u a l behavior and voltammetric r e c o r d  of each r a t a l l o w s a f i n e l y - g r a i n e d temporal catecholamine  efflux  vivo m i c r o d i a l y s i s voltammetric  i n these r e g i o n s d u r i n g s e x u a l b e h a v i o r .  i n the nucleus accumbens and s t r i a t u m .  S e v e r a l hypotheses  about  DA f u n c t i o n  i n male s e x u a l behavior  i n the g e n e r a l d i s c u s s i o n t o account  r e s u l t s of the p r e s e n t experiments. to f i t these r e s u l t s postulated  In  i s used s u b s e q u e n t l y to c o n f i r m the  results  were presented  a n a l y s i s of DA or  f o r the  A c a u t i o u s attempt  i n t o the g e n e r a l t h e o r e t i c a l  was made  framework  f o r m e s o t e l e n c e p h a l i c DA systems i n the c o n t r o l of  i n c e n t i v e m o t i v a t i o n and g o a l - d i r e c t e d b e h a v i o r , and f o r d i e n c e p h a l i c DA systems i n the neuroendocrine penile reflexes.  The c l i n i c a l  r e g u l a t i o n of  r e l e v a n c e of these r e s u l t s t o the  c o n t r o l of s e x u a l d e s i r e , a r o u s a l , and d y s f u n c t i o n i n human males was a l s o c o n s i d e r e d .  51 EXPERIMENT I: STATISTICAL ANALYSIS OF MALE SEXUAL BEHAVIOR IN THE BILEVEL CHAMBER  An important g o a l rats  of r e s e a r c h  on the s e x u a l  i s to understand the mechanisms  of male c o p u l a t i o n .  behavior of male  that c o n t r o l various  aspects  T h i s g o a l can be approached i n d i f f e r e n t  ways a t many l e v e l s of a n a l y s i s , but a l l r e q u i r e a taxonomy t h a t d i s t i n g u i s h e s v a r i o u s  formal  measures of s e x u a l  behavior.  The development of such a taxonomy depends upon the a n a l y s i s of normative data which allows behavior to be d e f i n e d mechanisms t h a t r e f l e c t  " b a s e l i n e " r a t e s of  copulatory  f o r m a l l y and o b j e c t i v e l y .  Conceptual  the deep s t r u c t u r e of male  copulatory  behavior can be generated from the a n a l y s i s of normative These c o n c e p t u a l  mechanisms can be assembled i n t o  models of s e x u a l  b e h a v i o r , many of which are u s e f u l  for  i d e n t i f y i n g p o t e n t i a l neural  hypothetical heuristically  mechanisms.  There a r e two types of h y p o t h e t i c a l models of male behavior. Toates  The f i r s t  (1986), t r i e s  behavior.  type,  data.  exemplified  sexual  by the model proposed by  to account f o r a l l p o s s i b l e f a c e t s of sexual  T y p i c a l l y , t h i s approach generates a l a r g e number of  conceptually  d i s t i n c t mechanisms t h a t are based, i n l a r g e  on the i n s p i r e d i n t u i t i o n of the o b s e r v e r .  part,  For example, i n  T o a t e s ' model, e j a c u l a t i o n depends upon s e v e r a l mechanisms  that  p r o c e s s the i n c e n t i v e q u a l i t i e s of the female, the i n t e r n a l s t a t e of s e x u a l  a r o u s a l , and the s e n s i t i v i t y to g e n i t a l s t i m u l a t i o n .  52 Each of these mechanisms, i n t u r n , can be acted upon by i n h i b i t o r y mechanisms t h a t d i s s i p a t e s e x u a l a r o u s a l , d e s e n s i t i z e the g e n i t a l s , and decrease (e.g., a f t e r e j a c u l a t i o n ) . t e s t a b l e hypotheses,  Although  models such as t h i s  they o f t e n do not s p e c i f y how  measures of s e x u a l behavior mechanisms.  the i n c e n t i v e value of the female generate  individual  are r e l a t e d t o the c o n c e p t u a l  For example, a decrease  i n the number of  i n t r o m i s s i o n s b e f o r e e j a c u l a t i o n may be viewed e i t h e r as an i n c r e a s e i n s e x u a l a r o u s a l , an i n c r e a s e i n s e n s i t i v i t y t o g e n i t a l s t i m u l a t i o n , s e n s i t i z a t i o n of a system t h a t f a c i l i t a t e s e m i s s i o n , a decrease of  in erectile capability,  or any  seminal  combination  these. The second type of model, e x e m p l i f i e d by the a n a l y s e s of  Beach (1956) and Sachs (1978), behavior  t r i e s t o reduce male s e x u a l  t o a minimum number of c o n c e p t u a l l y independent  mechanisms.  T h i s approach can be a i d e d by c e r t a i n  procedures.  For example, Beach used m u l t i p l e c o r r e l a t i o n s among  normative measures of male s e x u a l behavior  to determine both the  s t a b i l i t y and r e l a t i o n s h i p of those measures. helped  statistical  This a n a l y s i s  him i n f e r t h a t a minimum of two mechanisms c o n t r o l l e d the  s e x u a l behavior  of male r a t s : a s e x u a l a r o u s a l mechanism t h a t  c o n t r o l l e d both p r e c o p u l a t o r y i n v e s t i g a t i o n of the female and the i n i t i a t i o n of mounts, and an i n t r o m i s s i o n and e j a c u l a t i o n mechanism t h a t focused  the male's s e x u a l responses  e n t i r e l y on g e n i t a l s t i m u l a t i o n through until  e j a c u l a t i o n occurred.  almost  vaginal intromission  However, Beach presented  v e r y few of  53 the  intercorrelations  whether m u l t i p l e  in that  correlations  paper, and  thus i t i s not  were c a l c u l a t e d  clear  f o r a l l measures of  copulatory behavior. Sachs (1978) p r o v i d e d an q u e s t i o n of the  i n t e r e s t i n g s o l u t i o n to  minimum number of mechanisms i n v o l v e d  s e x u a l behavior of male r a t s by s u b j e c t i n g correlations  the  Ten  mount and  intromission  measured from the intromissions  periods of 22  first  I I I , and  respectively).  both the  first  The  Bermant (n = 74).  the  "hit rate"  the  and  (intromission  to the  termination  time from v o c a l i z a t i o n  intromission  after  ejaculation,  Sachs (n = 18),  from the  laboratories  B a r f i e l d (n = 23),  females. was  Although  given,  i n s m a l l square or  u n i l e v e l chambers under r e l a t i v e l y optimal c o n d i t i o n s dark phase of the  the  most of the data were taken  testing conditions  r a t s were t e s t e d  of  and  U n f o r t u n a t e l y , l i t t l e i n f o r m a t i o n about  i n f o r m a t i o n about the  d u r i n g the  latency  relative refractory  time from e j a c u l a t i o n  p r e s e n t e d , except t h a t  the  to  series:  number of mounts  a b s o l u t e and  r a t s ' second t e s t w i t h r e c e p t i v e  assumed t h a t  ejaculatory  ejaculation  the  i n t h r e e data s e t s  three i n v e s t i g a t o r s ,  s u b j e c t s was  multiple  i n t e r c o r r e l a t i o n s among those measures were  examined s e p a r a t e l y  from the  intromission,  v o c a l i z a t i o n , and  t e r m i n a t i o n to the  first  l a t e n c i e s , the  preceding e j a c u l a t i o n ,  (measured as the  kHz  the  measures of c o p u l a t o r y behavior were  i n Long-Evans r a t s through the  r a t i o ) , the  the  in  among normative measures of male s e x u a l b e h a v i o r  factor analysis. analyzed  the  circadian  light/dark  i t may  be  circular (e.g.,  cycle).  no  54  Several  c o r r e l a t i o n s among the measures of  behavior were found to be two  of the  statistically significant  three data s e t s .  were c o r r e l a t e d ,  Mount and  as were the  number of mounts and  ratio.  latency,  a b s o l u t e r e f r a c t o r y phase, and  L i k e w i s e , the  I I I was  ejaculation  a b s o l u t e r e f r a c t o r y phase and PEI  was  correlated  correlated  latency  was  the  the  a b s o l u t e and  ejaculation  total  correlated  least  latencies  with the  the t o t a l PEI.  with both the  i n at  intromission  intromission the  The  copulatory  PEI.  with  the  Finally,  the  total  relative  refractory  phases. Subsequent f a c t o r a n a l y s i s using  orthogonal  of the  (varimax) r o t a t i o n s  accounted f o r over 90%  of the  significant  revealed  variance.  was  f a c t o r t h a t accounted  f o r the  was  termed the  the  I I I , the  and  the  copulatory  largest proportion factor.  This  The  rate factor.  This  was  moderately by the  largest proportion  rate factor. the  the  This  f a c t o r was  intromission  variance loaded  ratio.  was  second  arousal  intromission  accounted f o r by  loaded h e a v i l y by The  by  period,  r e l a t i v e refractory period.  of the v a r i a n c e  on  initiation  f a c t o r , r e m i n i s c e n t of Beach's s e x u a l  l a t e n c i e s , and  mounts and  f a c t o r was  called  loaded h e a v i l y by mount and  hit  of the  f a c t o r t h a t accounted f o r the  of the v a r i a n c e  that  The  absolute r e f r a c t o r y  mechanism, was  third  each f a c t o r .  largest proportion  the  factors  loaded most h e a v i l y  accounted f o r by)  ejaculation latency,  t o t a l PEI.  four  These f a c t o r s were g i v e n  t e n t a t i v e names based on the measures t h a t ( i . e . , whose v a r i a n c e  correlations  fourth  the  largest  The the  number of proportion  55 of the v a r i a n c e factor.  This  was  accounted f o r by an  f a c t o r , reminiscent  e j a c u l a t i o n mechanism, was and  intromission  count  of Beach's i n t r o m i s s i o n  loaded  by the number of  and  intromissions  the r e l a t i v e r e f r a c t o r y p e r i o d . At  first  glance,  i t would seem t h a t the measures  contained  w i t h i n each f a c t o r share common c o n t r o l l i n g mechanisms. as Sachs p o i n t e d  out,  However,  t h i s does not mean t h a t the mechanisms  i n d i v i s i b l e or the measures redundant. t h a t f a l l w i t h i n a s i n g l e f a c t o r can  In f a c t , c e r t a i n measures  be d i s s o c i a t e d with  appropriate  p h a r m a c o l o g i c a l or n e u r o s u r g i c a l  the PEI  the e j a c u l a t i o n l a t e n c y ; B a r f i e l d , Wilson, &  and  McDonald, 1975;  Clark, Caggiula,  Pfaus & P h i l l i p s , copulatory factors  1987).  behavior can  invalid.  The  of mounts with and  McConnell, & Antelman,  1975;  f a c t t h a t c e r t a i n measures of  the  without  conceptual  initiation  render  mechanisms  of c o p u l a t i o n ,  i n t r o m i s s i o n , and  intromissions  before  of the s e x u a l  behavior of male r a t s .  the  f a c t o r a n a l y s i s to d e r i v e c o n c e p t u a l  f o r being  the  the  information  r e s u l t s can  was  behavior was  the  ratio  i n any  first  mechanisms of male  are s e v e r a l m e t h o d o l o g i c a l q u e s t i o n s  be addressed before  (reflecting  the number of  e j a c u l a t i o n ) must be c o n s i d e r e d  Although t h i s study i s l a u d a b l e  which s e x u a l  (e.g.,  Simply, the r e s u l t s of Sachs' a n a l y s i s suggest  the r a t e of c o p u l a t i o n ,  above, no  the  treatments  be d i s s o c i a t e d does not  that a minimum of four g e n e r a l  behavior, there  are  be g e n e r a l i z e d .  to  model  use  sexual  t h a t need to As  mentioned  provided  about the c o n d i t i o n s  under  tested.  E s t i m a t e s of communality were  56  made f o r Sachs' and sample.  T h i s was  B a r f i e l d * s samples, but not  an u n f o r t u n a t e  omission  B a r f i e l d ' s samples were r e l a t i v e l y s m a l l  f o r Bermant's  because S a c h s (ns = 18 and  r e s p e c t i v e l y ) whereas Bermant's sample was  23,  much l a r g e r (n =  There were a l s o s e v e r a l i n c o n s i s t e n c i e s r e g a r d i n g the c e r t a i n measures of c o p u l a t o r y behavior  and  1  74).  l o a d i n g of  on the four f a c t o r s .  For  example, i n Bermant's sample, the number of mounts, the I I I , and the e j a c u l a t i o n l a t e n c y loaded i n Sach's and  onto the  initiation  B a r f i e l d ' s samples they d i d not.  factor  whereas  It i s impossible  to determine whether the d i f f e r e n t number of s u b j e c t s or  any  p o s s i b l e d i f f e r e n c e s i n t e s t i n g procedure c o n t r i b u t e d to  the  inconsistent analyses  loadings.  F i n a l l y , Sachs noted  t h a t none of  took the c o n t r i b u t i o n of the female's behavior  consideration.  Given  behavior  female can a l t e r the c o p u l a t o r y behavior  of the  evidence  important  into  t h a t the s o l i c i t a t i o n and  male (Madlafousek & H l i n a k , 1978;  McClintock,  the  pacing of  the  1984), i t i s  to c o n t r a s t measures of male c o p u l a t o r y behavior  c o n d i t i o n s i n which the females can c o n t r o l the  in  sexual  interactions. The  b i l e v e l chambers designed  by Mendelson and  (1987) p r o v i d e an o p p o r t u n i t y to assess  Gorzalka  the c o p u l a t o r y  behavior  of male r a t s i n a s i t u a t i o n where the female can pace the copulatory contact. l e v e l s e v e r a l times by the male. reminiscent  T y p i c a l l y , a female r a t runs from l e v e l  to  i n these chambers f o l l o w i n g each i n t r o m i s s i o n  T h i s behavior  f o r c e s the male to chase her and  of the c h a s i n g behavior  observed  is  i n male r a t s given  access  to r e c e p t i v e females i n a l a r g e open f i e l d  1984).  P r e l i m i n a r y evidence  male c o p u l a t o r y behavior  suggests  are a l t e r e d  For example, the number of mounts and  (McClintock,  t h a t c e r t a i n measures of i n the b i l e v e l  chambers.  i n t r o m i s s i o n s t h a t precede  e j a c u l a t i o n appears to be lower i n the b i l e v e l chambers than the t r a d i t i o n a l u n i l e v e l chambers  ( i n which females do  d i s p l a y complex p a t t e r n s of p a c i n g b e h a v i o r ) . e j a c u l a t i o n l a t e n c y and chambers than  PEI  t h e s i s to analyze  measure of a n t i c i p a t o r y s e x u a l m o t i v a t i o n ,  the  Because i t  l e v e l changing as a  i t was  necessary  examine the s e x u a l behavior  of male r a t s i n the b i l e v e l  i n more d e t a i l .  i n the f i r s t  Therefore,  both  bilevel  i n the t r a d i t i o n a l u n i l e v e l chambers.  i s d e s i r a b l e i n the p r e s e n t  not  Likewise,  appear s h o r t e r i n the  in  experiment of  to  chambers this  thesis,  i n t e r c o r r e l a t i o n s among 11 measures of s e x u a l  behavior  derived  from 80 male r a t s t h a t had  asymptotes  reached  individual  of s e x u a l performance were s u b j e c t e d to f a c t o r a n a l y s i s .  Method Subjects  and  Surgery  Female and  male Long-Evans r a t s were obtained  R i v e r Canada, Inc., S t . Constant, sex  They were housed  i n groups of s i x i n 18x25x65 cm wire mesh cages i n a  room maintained approximately  on a r e v e r s e d  21°C.  i n the home cages. via  Quebec.  from C h a r l e s  Food and The  by  colony  12 h l i g h t / 1 2 h dark c y c l e at water were c o n t i n u o u s l y a v a i l a b l e  females were b i l a t e r a l l y  ovariectomized  lumbar i n c i s i o n s under sodium p e n t o b a r b i t a l a n e s t h e s i a  58 ( S o m n i t a l , 40 mg/kg) and allowed a t l e a s t one week of r e c o v e r y before t e s t i n g .  Sexual r e c e p t i v i t y was induced i n the females by  subcutaneous  (SC) i n j e c t i o n s of e s t r a d i o l benzoate  progesterone  (500 ug) 48 h and 4 h, r e s p e c t i v e l y , b e f o r e each  test  (10 ug) and  i n which they p a r t i c i p a t e d as s t i m u l u s females.  The housing  c o n d i t i o n s f o r a l l r a t s , and the s u r g e r y and s t e r o i d - p r i m i n g regimen  f o r the s t i m u l u s females, were used throughout the  experiments  reported i n t h i s  thesis.  Apparatus The t e s t i n g chambers used  i n t h i s study were s i m i l a r t o  those d e s c r i b e d by Mendelson and G o r z a l k a (1987).  Each  was c o n s t r u c t e d of P l e x i g l a s with o u t s i d e dimensions cm.  chamber  of 51x70x15  The narrowness of the chambers f o r c e d animals t o mate with  their  f l a n k s t o the o b s e r v e r , the o p t i m a l o r i e n t a t i o n f o r  e v a l u a t i n g the s e x u a l behavior of r a t s .  However, the chambers  were not so narrow as t o prevent animals from t u r n i n g freely  inside.  about  A p l a t f o r m 40 cm i n l e n g t h , c e n t e r e d , and s e t 28  cm above the f l o o r , d i v i d e d  each chamber i n t o two l e v e l s .  A set .  of ramps and narrow l a n d i n g s a t each end of each the chamber allowed animals t o move f r e e l y from one l e v e l t o another. Behavioral Testing  Procedures  E i g h t y males (450 t o 700 g) were g i v e n 10 s c r e e n i n g t e s t s f o r masculine c o p u l a t o r y b e h a v i o r . i n d u r a t i o n and were conducted third  of the dark c y c l e .  S c r e e n i n g t e s t s were 25 min  one every 4 days d u r i n g the middle  During these s c r e e n i n g t e s t s , each male  was p l a c e d i n t o one of the b i l e v e l chambers f o r a 5-min t e s t of  59 level into  changing a f t e r t h e chamber  change, mount, computerized (1)  (4)  The o c c u r r e n c e  intromission,  and e j a c u l a t i o n  event recorder  the next (8)  (9)  mount o r  (EL;  time  (6)  (time  (7)  ejaculation  (NI)  intromission  reinitiation each o f  the  within  total  of last  screening t e s t . statistical  latency/the (IR);  number o f  for  number  of  t h e number  of  mounts w i t h  number o f  and  ejaculations  inclusion:  the presentation  of  the  first  the  intromission;  10 m i n o f  tests.  was c o n d u c t e d test  test,  stable  test  rates  female; and  the  ejaculation,  A final  (NM)  each  period;  The d a t a f r o m t h i s  analysis.  to  5-min a d a p t a t i o n  three screening behavior  prior  to  mounts  By t h e t e n t h b a s e l i n e  intromission within  masculine copulatory  from e j a c u l a t i o n  ratio  the t o t a l  (NE).  15 m i n o f  and  introduction  t h e number o f  the  5 min of  from the  mount  to  (10)  intromission within  (3)  intromission  (the e j a c u l a t i o n  changing during the  (LCD;  (2)  from the f i r s t  80 m a l e s had r e a c h e d t h e c r i t e r i a level  measures:  (5)  III  20-min t e s t  following  on a  in seconds);  t h e PEI  (11)  level  5-min p e r i o d ;  time  the  and  placed  intromission  intromissions  intromission);  each  was r e c o r d e d  changes  (ML and I L ;  intromission/the  in the  in the  level  in seconds);  t h e number o f  mounts w i t h  of  latency  i n seconds.);  intromissions);  achieved  first  intromission  ejaculation;  without  initiate  (LC)  f e m a l e was  of  which d e r i v e d the  changes  latencies  female t o the  the e j a c u l a t i o n  all  level  i n seconds t o  ejaculation  receptive  20 m i n .  intromission  of the  and  for  t h e number o f  latency  which a s e x u a l l y  on  of  4 days a f t e r  were s u b j e c t e d  the to  last  60 Statistical  Analysis  Means, standard e r r o r s , and  i n t e r c o r r e l a t i o n s among the  measures of s e x u a l behavior were c a l c u l a t e d available s t a t i s t i c a l StatSoft,  Tulsa,  same s t a t i s t i c a l  OK).  Factor  analysis  package u s i n g  Sachs  a  package (Complete S t a t i s t i c a l was  orthogonal  comercially System,  conducted with  the  (varimax) r o t a t i o n s  the m a t r i c e s of c o r r e l a t i o n c o e f f i c i e n t s . method used by  using  11  This  reproduced  of  the  (1978).  Results  and  Discussion  Correlations The  means, standard e r r o r s , and  i n t e r c o r r e l a t i o n s among  11 measures of s e x u a l behavior d e s c r i b e d Table I.  C o r r e l a t i o n c o e f f i c i e n t s that  on Page 59 are had  a  s i g n i f i c a n c e of p_<.05 are shown i n Table I I . interesting  f i n d i n g i n t h i s a n a l y s i s was  The  most  t h a t LC d i d  of the  behavior.  from measures t h a t  used to  i n f e r s e x u a l m o t i v a t i o n , e.g.,  however, was NM,  and  (<.26).  NI,  correlated although the  This  mounting may  was  vaginal  p o s i t i v e l y and  not  be  other measures of  the  the  or IL.  and  during  typically  The  LCL  Consistent  ML,  small  i n i t i a t i o n of l e v e l changing  and  with  IL were h i g h l y p o s i t i v e l y c o r r e l a t e d .  expected because h i g h l y t r a i n e d intromission  ML  are  sexual  s i g n i f i c a n t l y with the  independent p r o c e s s e s . ML  not  c o r r e l a t i o n c o e f f i c i e n t s were  indicates that  Sachs' a n a l y s i s , the This  LC  shown i n  statistical  c o r r e l a t e s i g n i f i c a n t l y with any This d i s t i n g u i s h e s  the  their f i r s t  rats usually  gain  or second mount.  61  Table  I  Means, s t a n d a r d e r r o r s , and i n t e r c o r r e l a t i o n s among t h e 11 measures of s e x u a l b e h a v i o r d i s p l a y e d by male r a t s l n the b i l e v e l chambers.  Mean  LC  LCL  ML  IL  EL  11.21  18.00  13.80  17.31  286. 66 270.04 4.22  .35  1.46  1.64  1.96  SEM  14. 09  PEI  NM  5.87  .32  NI  NE  IR  III  10.75  2.47  .74  26. 99  .37  .07  .01  1. 17  -.32  -  Correlations LC LCL  -.18  ML  -.04  + .25  IL  -.01  + .17  + .87  EL  -.06  + .11  -.05  -.07  PEI  + .12  -.06  + .05  + .01  + .43  NM  -.10  + .22  + .01  + .04  + .42  + .27  -  NI  -.03  + .25  -.13  -.12  + .54  + .11  + .46  NE  -.10  -.02  -.15 - -.16  -.50  -.28  - .24  -.35  IR  + .15  -.19  -.15  -.20  -.26  -.26  - .84  -.06  + .12  III  -.08  -.01  + .10  + .07  + .76  + .44  + .23  -.09  -.29  Table Correlation coefficients Correlated  with s t a t i s t i c a l  significance  R(X,Y)  P.  LCL x ML  + .254  .022  LCL x NM  + .223  .044  LCL x NI  + .249  .025  ML x I L  + .875  .000  EL x PEI  + .432  .000  EL  NM  + .416  .000  EL x NI  + .541  .000  EL x NE  -.503  .000  EL x IR  -.257  .020  EL  III  + .758  .000  PEI x NM  + .268  .015  PEI  NE  -.277  .013  PEI x IR  -.264  .017  PEI x  + .436  .000  NM x NI  + .465  .000  NM x NE  -.239  .031  NM x IR  -.843  .000  NM x  + .226  . 041  -.345  .001  -.317  .004  X  X  X  NI  X  IR  X  measures  II  III  III NE III  of  p_<.05.  63  Sachs r e p o r t e d the in  t h a t the EL was p o s i t i v e l y c o r r e l a t e d  with  I I I and the PEI i n h i s and B a r f i e l d ' s d a t a , and with the NM Bermant's d a t a .  Those t h r e e c o r r e l a t i o n s were r e p l i c a t e d ,  although the c o e f f i c i e n t s were g e n e r a l l y study  smaller  (as they were i n Bermant's sample).  i n the p r e s e n t  However, t h r e e other  measures were c o r r e l a t e d w i t h the EL i n the p r e s e n t s t u d y  that  were e i t h e r not e v a l u a t e d or d i d not reach s i g n i f i c a n c e i n Sachs' analysis. IR.  The EL was n e g a t i v e l y  The f i r s t  ejaculations  c o r r e l a t e d with the NE and the  of these was expected because the number of  possible  to each e j a c u l a t i o n  i n a 20-min t e s t decreases as the l a t e n c y  increases.  However, the n e g a t i v e c o r r e l a t i o n  between the EL and the IR r e q u i r e s At  first  amore e x t e n s i v e  g l a n c e , t h i s c o r r e l a t i o n would seem t o i n d i c a t e t h a t the  r e l a t i v e number of i n t r o m i s s i o n s ejaculate.  p r e d i c t s the l a t e n c y t o  However, the EL was a l s o p o s i t i v e l y c o r r e l a t e d  the NI i n the present study.  This  r e l a t i v e l y larger  increase  the decrease i n the IR.  i n mounts over i n t r o m i s s i o n s  i n the p r o p o r t i o n  a s i t u a t i o n t h a t could  f a i l u r e to g a i n  causes  of mounts without  indicate either a r e l a t i v e  erection, penile desensitization,  PEI was p o s i t i v e l y c o r r e l a t e d  Sachs' a n a l y s i s .  suggests t h a t a  Thus longer ELs i n these r a t s may be  accompanied by an i n c r e a s e intromission,  with  c o r r e l a t i o n , t o g e t h e r with the  p o s i t i v e c o r r e l a t i o n between the EL and the NM,  The  explanation.  or f a t i g u e .  with the I I I , as i t was i n  However, i n the present study, the PEI was  positively correlated  with the NM,  i n d i c a t i n g that  d i s p l a y i n g more mounts without i n t r o m i s s i o n  animals  a l s o have longer  also  64 latencies  to r e i n i t i a t e  intromission  after  ejaculation.  was n e g a t i v e l y c o r r e l a t e d w i t h b o t h t h e NE and t h e present  study.  described  for  The f i r s t  t h e EL and NE,  d e c r e a s e t h e number o f The s e c o n d n e g a t i v e that  animals w i t h  increase longer  to  ejaculate  experience  either  IRs  longer  PEIs would  achieved  to  of  p a t t e r n c o u l d occur  a  relative may t a k e  following  in animals  penile  test.  suggests  intromission)  intromission  that  likely  i n a 20-min  (presumably a f u n c t i o n  dysfunction,  the  is s i m i l a r  b e t w e e n t h e PEI and IR  and r e i n i t i a t e  erectile  IR i n  that  desensitization,  fatigue.  the present IR,  other study.  present  correlations  f o u n d b y Sachs were r e p l i c a t e d  The NM was h i g h l y n e g a t i v e l y c o r r e l a t e d  i n agreement w i t h t h e a n a l y s i s  the p o s i t i v e  this  correlation  Again, t h i s  Several  the  in that  ejaculations  lower  correlation  i n t h e number o f mounts w i t h o u t  ejaculation.  or  negative  The PEI  correlation  study replicated  c o r r e l a t i o n was n o t  samples.  positively  that  correlated  in either  Sachs'  or  b e t w e e n t h e NM and o t h e r found  i n Sachs'  in  Although the  Barfield's measures  presented  w i t h t h e NE and t h e  correlated  with the  Both of these c o r r e l a t i o n s  consistent  w i t h the analysis  III.  presented  above.  IR was  with  above.  study.  was n e g a t i v e l y c o r r e l a t e d  in  The NM was  w i t h t h e NI and n e g a t i v e l y c o r r e l a t e d  were f o u n d i n t h e p r e s e n t  with  sample,  analysis.  i n agreement w i t h t h e a n a l y s i s  correlations  III  found i n Bermant's data  evident  s t u d y were n o t  t h e NE, a g a i n Two o t h e r  b e t w e e n t h e NM and t h e  Two c o r r e l a t i o n s  the present  presented above.  in  The NI  negatively are  65 The p i c t u r e the  idea t h a t  intromissions low IRs,  that  emerges f r o m t h e  animals t h a t  t h u s be i n f e r r e d  chambers a r e l i k e l y  E L s , and P E I s ,  that  animals  short  Factor  Ills,  that  factors  to allow d i r e c t  p r e s e n t e d by S a c h s .  were e x t r a c t e d ,  intersubject  common p r a c t i c e ,  .30  variance)  (i.e.,  variance  1973).  that  were a l s o  Estimates  high  the  all  measures.  ignored.  III,  of  for  eight 95% o f  According  factor  the  to  loadings  l e s s t h a n 9% o f t h a t  The f i v e  factors  that  (e.g., of  less  measure's  emerged were  w i t h t h o s e d e s c r i b e d b y Sachs and were  These f a c t o r s  factor  and t h e i r  major  l o a d e d most variable  IV.  in this  a n a l y s i s was l o a d e d by  E L , P E I , and NE.  copulatory rate  comparison  f a c t o r s were i g n o r e d  Measures w i t h  a r e shown i n T a b l e  The s t r o n g e s t measures:  A total  names based on t h e measures t h a t  h e a v i l y onto each. loadings  for  analysis  of. communality  of which accounted  accounted f o r  remarkably consistent given t e n t a t i v e  five  the remaining three  Hakstian & Muller,  1  smaller  ejaculations.  m a t r i x was s u b j e c t e d t o f a c t o r  each measure a r e shown i n T a b l e I I I .  Sachs  may  Analysis  with the factors  than  It  i n t h e s e chambers d i s p l a y  using normalized varimax r o t a t i o n s  total  and  display  display a relatively  E L s , and P E I s , and many  The c o r r e l a t i o n  for  also to  and f e w e j a c u l a t i o n s .  number o f mounts and i n t r o m i s s i o n s IRs,  supports  d i s p l a y a l a r g e number o f mounts  in the b i l e v e l  long I l l s ,  intercorrelations  factor,  This  factor,  accounted f o r  similar  four to  more t h a n 26% o f  the  Table Estimates of communality f o r Measure  III  each measure o f s e x u a l Communality  LC  .141  LCL  .253  ML  .791  IL  .789  EL  .963  PEI  .284  NM  .908  NI  .935  NE  .372  IR  .887  III  .946  behavior  67  Table F a c t o r s and t h e i r  IV variable  loadings  Factor  Measure  1 . C o p u l a t o r y Rate  III  +.948  EL  +.853  PEI  +.461  NE  -.390  % variance  26  ML  +.909  IL  +.907  % variance  22  IR  +.905  NM  -.876  % variance  21  NI  +.945  EL  +.464  NE  -.391  NM  +.331  % variance  18  LCL  +.462  LC  -.456  % variance  8  2.  Initiation  3. H i t Rate  4 . Mount Count  5. A n t i c i p a t i o n  r  Variable  Loading  68 intersubject factor  variance  was l o a d e d b y t h e  The a d d i t i o n indicates rate.  of  that  III,  of  the  to that  +.75).  for  Sachs'  factor  in the present  factor  loadings  In addition,  a larger  results  the b i l e v e l copulatory  chambers rate  noted above, copulatory  of  of  factor  less  Sachs'  proportion  that  of  of  analysis  in t r a d i t i o n a l  subprocesses  that  rate  factor  the  from  to  in  the  chambers.  the  As  the  appropriate  important  the copulatory  (between  o f male r a t s  contribute  is therefore  factor  rate  different  with  and  analysis  variance  unilevel  c a n be d i s s o c i a t e d  EL,  although the  Nevertheless,  t h e measures t h a t  suggestion that  copulatory  III,  copulatory  rate PEI.  in the present  the copulatory  It  the  the t o t a l  not q u a l i t a t i v e l y  manipulations.  Sachs'  may c o n s i s t  is  rats  several  rate  experimental reiterate  suggest  for  r e p o r t e d by Sachs,  37% and 43% i n t h e t h r e e d a t a s a m p l e s ) . present  copulatory  E L , a b s o l u t e P E I , and t o t a l  t h e PEI was c o n s i d e r a b l y  (+.46 versus accounted  measures.  t h e NE may a l s o be u s e d as a m e a s u r e o f  PEI was i d e n t i c a l for  all  t h e NE t o t h i s  The r e l a t i o n  loading  for  rate  to  o f male  are normally coordinated  rats  during  copulation. An i n i t i a t i o n This  factor  22% o f  the  factor  was a l s o  found  analysis.  was l o a d e d h e a v i l y b y t h e ML and I L and a c c o u n t e d intersubject  and B a r f i e l d ' s this  factor,  bout  of  variance  data samples,  suggesting that  for  however,  all  copulation after  measures.  Unlike  t h e PEI d i d n o t  the process  c o p u l a t i o n may i n d e e d be d i s t i n c t  reinitiates  in the present  that  load  initiates  each e j a c u l a t i o n ,  an i d e a  Sachs' onto  the  from the process  for  first that  first  69  presented  f o r m a l l y by M c G i l l  The t h i r d  largest  factor,  almost  21% o f  the t o t a l  rate  hit  factor.  This  18% o f  related  be d i s t i n g u i s h e d of  the b i l e v e l  sample,  measures.  analysis,  load  however,  and w e r e  for  The PEI  across  t h e PEI d i d n o t  t o one a n o t h e r  factor  intersubject from Sachs'  his onto  t h e NM and  essentially  was l o a d e d b y t h e N I , E L , NE,  variance  for  intromission  for  in t r a d i t i o n a l  by t h e  their  fact  that  more e f f i c i e n t l y  A l t h o u g h t h e EL and NE a l s o  all count  accounted  measures. factor  relationship  underlie  for It  by  the  unilevel  PEI.  female r a t s  chambers, can pace  in the b i l e v e l  is  the t o t a l  possible  e x p l a n a t i o n w o u l d be c o n s i s t e n t  rate  of  in  and the  chambers. rate  that  mounting  are  copulation.  the copulatory  count and  distinct This  w i t h the suggestion noted  b y Sachs c o n c e r n i n g s u b p r o c e s s e s w i t h i n  can  the  t o t h e NI and NM makes t h e mount It  and  occur d i f f e r e n t l y  p e r se a r e d r i v e n by mechanisms t h a t  from those t h a t  of  loaded onto the c o p u l a t o r y  conceptually different.  intromitting  factor,  m o u n t i n g and i n t r o m i t t i n g  chambers, t h a n  copulatory contact  factor.  all  accounted  but not r e l i a b l y  t e r m e d t h e mount c o u n t  that  may be a c c o u n t e d  factor  factor,  for  factor,  t h e E L , NE, and NM, and t h e e x c l u s i o n  This suggests  factor,  rate  variance  As i n S a c h s '  largest  factor,  the t o t a l  addition  rate  hit  This  measures.  The f o u r t h NM.  t o Sachs'  In the present  IR w e r e n e g a t i v e l y redundant  was l o a d e d b y t h e NM and I R .  intersubject  loaded onto Sachs'  the h i t  factor  identical  data samples.  (1965).  above  rate  70 The f i f t h  f a c t o r was  loaded  by LC and the LCL.  This factor,  termed the a n t i c i p a t i o n f a c t o r , accounted f o r s l i g h t l y more than 8% of the t o t a l  intersubject variance  f o r a l l measures.  The  e x t r a c t i o n of t h i s f a c t o r complements the f i n d i n g t h a t LC does not c o r r e l a t e s i g n i f i c a n t l y with behavior  and supports  other measures of c o p u l a t o r y  the c o n c l u s i o n t h a t t h i s measure i s both  c o n c e p t u a l l y and s t a t i s t i c a l l y d i s t i n c t the  from those  t h a t measure  i n i t i a t i o n of c o p u l a t i o n , e.g., the ML or I L . There are s e v e r a l important  results.  First,  the e x t r a c t i o n of f i v e f a c t o r s suggests t h a t a  minimum of f i v e c o n c e p t u a l adequate e x p l a n a t i o n  rate,  mechanisms are necessary  of male c o p u l a t o r y behavior  chambers: a n t i c i p a t i o n , mount count.  i m p l i c a t i o n s of the p r e s e n t  f o r an  i n the b i l e v e l  i n i t i a t i o n , c o p u l a t o r y r a t e , h i t r a t e and  The f a c t t h a t t h r e e of these  factors  i n i t i a t i o n , and h i t r a t e ) aire v i r t u a l l y  (copulatory  identical  to those  found by Sachs (1978) suggests t h a t measures of c o p u l a t o r y behavior  are r e l a t i v e l y s t a b l e i n w e l l - t r a i n e d r a t s ,  of the type  of t e s t i n g chamber  used.  However, the mount count  f a c t o r was c o n c e p t u a l l y and s t a t i s t i c a l l y d i f f e r e n t i n t r o m i s s i o n count f a c t o r .  regardless  from S a c h s  1  T h i s i n d i c a t e s t h a t the d i s p l a y of  mounts and i n t r o m i s s i o n s i n the b i l e v e l chambers i s d i f f e r e n t from the d i s p l a y of those chambers.  behaviors  i n the t r a d i t i o n a l  unilevel  As noted above, t h i s d i f f e r e n c e may be due to the f a c t  t h a t female r a t s can pace the c o p u l a t o r y c o n t a c t more e f f i c i e n t l y i n the b i l e v e l chambers. by the male i s p r o b a b l y  The p a t t e r n of mounts and i n t r o m i s s i o n s v e r y s e n s i t i v e to the p a c i n g  behavior  of  the  female.  This hypothesis  c o u l d be examined d i r e c t l y  b i l e v e l chambers by g i v i n g males access females t r e a t e d with the DA a n t a g o n i s t  to sexually receptive h a l o p e r i d o l (to eliminate  p r o c e p t i v e s o l i c i t a t i o n and p a c i n g b e h a v i o r ) . important measures  to examine whether other  i n the  I t would a l s o be  potential anticipatory  (e.g., r a t e s of bar p r e s s i n g f o r secondary r e i n f o r c e r s  a s s o c i a t e d with the p r e s e n t a t i o n of a r e c e p t i v e female;  Everitt  et a l . , 1987) c o r r e l a t e with LC and load onto a common anticipation factor. The i n t e r c o r r e l a t i o n s among a l l the measures of s e x u a l behavior  except LC i n d i c a t e t h a t some of these measures are not  independent s t a t i s t i c a l l y ,  although  they may indeed be  independent c o n c e p t u a l l y or n e u r o b i o l o g i c a l l y . very  important  issue.  This r a i s e s a  Experiment-wise or Type 1 e r r o r i s  e l e v a t e d beyond the .05 c r i t e r i o n when r e l a t e d measures a r e analyzed  as though they a r e independent  statistical  analyses  (as i s the case i n most  of male c o p u l a t o r y b e h a v i o r ) .  of i n t e r c o r r e l a t i o n s among the measures of male behavior error. being  The e x i s t e n c e  copulatory  r e q u i r e s t h a t steps be taken t o reduce the e l e v a t e d The s o l u t i o n t o t h i s problem l i e s  asked.  i n the type  of q u e s t i o n  M u l t i p l e u n i v a r i a t e or nonparametric s t a t i s t i c s a r e  t y p i c a l l y used i n experiments t o analyze  treatment e f f e c t s on  i n d i v i d u a l measures of s e x u a l  This  behavior.  is justified in  s i t u a t i o n s where the outcome v a r i a b l e s a r e " c o n c e p t u a l l y independent"; where the r e s e a r c h being conducted i n nature  i s exploratory  ( i . e . , when new treatment or outcome v a r i a b l e s a r e  72 being a s s e s s e d ) ; been s t u d i e d  where some or a l l of the outcome v a r i a b l e s have  previously  i n u n i v a r i a t e contexts;  i n t e r e s t to show t h a t two equivalent & Morris, sexual  with respect 1989).  or where i t i s of  or more treatment c o n d i t i o n s  are  to a number of outcome v a r i a b l e s  (Huberty  However, because many of the measures of male  behavior are c o r r e l a t e d , experiment-wise e r r o r w i l l  elevated  be  i f s e p a r a t e u n i v a r i a t e a n a l y s e s are conducted f o r each  measure.  In these c a s e s , f u l l  should be a p p l i e d  or p a r t i a l B o n f e r r o n i  to the m u l t i p l e  u n i v a r i a t e or  corrections  nonparametric  0  t e s t s to reduce experiment-wise e r r o r by e l e v a t i n g the s i g n i f i c a n c e required  f o r each t e s t (e.g.,  level  of  Pfaus & P h i l l i p s ,  1989). The  second s o l u t i o n to the problem of e l e v a t e d  wise e r r o r  i s to use  multivariate s t a t i s t i c s .  addressed by t h i s s t a t i s t i c a l from those addressed analyses.  The  experimentquestions  t e c h n i q u e , however, are d i f f e r e n t  in multiple  u n i v a r i a t e or  nonparametric  M u l t i v a r i a t e s t a t i s t i c s are g e n e r a l l y concerned w i t h  o v e r a l l treatment e f f e c t s and  are used e i t h e r to determine  subgroups of outcome v a r i a b l e s t h a t account f o r the s i g n i f i c a n c e of treatment c o n d i t i o n s  or to determine the  of d i f f e r e n t outcome v a r i a b l e s r e q u i r e a n a l y s i s of the variables  (Huberty & M o r r i s ,  associated  i n each subgroup, both of which  i n t e r c o r r e l a t i o n s among the  m u l t i v a r i a t e procedures can constructs  relative contribution  1989). be  with the  outcome  Like factor anlaysis,  used to  identify  underlying  obtained m u l t i v a r i a t e r e s u l t s  thus p r o v i d e a t h e o r e t i c a l framework f o r i n t e r p r e t a t i o n .  The  and  experiment-wise e r r o r matrix; therefore  i s held at  .05  f o r the  entire  multivariate  a significant overall multivariate F  indicates  t h a t the subsequent a n a l y s i s of s i g n i f i c a n t simple or i n t e r a c t i o n effects within  the m u l t i v a r i a t e  experiment-wise e r r o r . the p s y c h o l o g i c a l test  followed  For  framework does not  t h i s reason, i t i s somewhat common i n  l i t e r a t u r e to see  by m u l t i p l e  composites of the  a significant multivariate  u n i v a r i a t e analyses instead  outcome v a r i a b l e s  linear discriminant  functions).  (e.g.,  canonical  Such a s t r a t e g y  " p r o t e c t " the u n i v a r i a t e a n a l y s e s from e l e v a t e d e r r o r , even though the questions.  of l i n e a r variates  i s used  or  to  experiment-wise  t e s t s themselves address v e r y d i f f e r e n t  However, f i n d i n g a s i g n i f i c a n t o v e r a l l m u l t i v a r i a t e  e f f e c t does not of m u l t i p l e 1984).  elevate  guarantee Type 1 e r r o r p r o t e c t i o n w i t h i n  univariate tests  Bonferroni  (Huberty & M o r r i s ,  corrections  are s t i l l  1989;  a matrix  Share,  n e c e s s a r y i n those  cases. I t seems r e a s o n a b l e to base the c h o i c e procedure on the q u e s t i o n s to be answered.  of a  statistical  I f i t i s of i n t e r e s t  to s e l e c t or order a s e t of outcome v a r i a b l e s , or to i d e n t i f y underlying be done.  variable constructs,  then m u l t i v a r i a t e a n a l y s e s should  I f i t i s of i n t e r e s t to a n a l y z e treatment e f f e c t s  each measure s e p a r a t e l y , conceptually  independent or the r e s e a r c h  n a t u r e , then m u l t i p l e be done, provided wise e r r o r .  e i t h e r because the measures  The  i s of an  on  are  exploratory  u n i v a r i a t e or nonparametric a n a l y s e s should  t h e y are c o r r e c t e d  for elevated  a p p l i c a t i o n of e i t h e r one  experiment-  of these t e c h n i q u e s  would b e n e f i t  t h e s t u d y o f male s e x u a l b e h a v i o r  r e d u c i n g Type 1  behavior  purpose of  the present  the r e s u l t s  framework  interpretation  factors  derived  mechanisms, well  the  provide  in this  framework  of  present  the measures.  by Sachs. contact  The f a c t  easily  unilevel  intromissions A second  of  the LCL).  behavior earlier  that is  anticipatory  The e x t r a c t i o n  strongly  suggests  are d i s t i n c t . suggestions  and p u r s u i t  of  the  (Sachs & B a r f i e l d , intromissions  of  that  This  these  hypothesis  1976)  into  by t h e m a l e .  of  the  small  the  s t u d y was  of  and  (Beach,  search, 1956)  initiation  The s e p a r a t i o n  of  the  female.  the (LC and initiation  copulatory  is consistent  the precopulatory  f e m a l e summates  to  sexual motivation  facets  found  and  separate a n t i c i p a t i o n  that  the  escape f r o m  mounts  in the present  in  copulatory  to the pacing behavior  difference  measures of  of  remarkably  factor  (in contrast  pattern  conceptual  factor  count  females cannot  that  important  c a n pace t h e  chambers  the temporal  sensitive  An  intromission  the  behavior  extent  c a n be v i e w e d as  a mount c o u n t  female r a t s  in which the  important  inclusion  that  the  in the b i l e v e l  chambers  suggests  factors  instead of  of  male  was n o t  To t h e  (1978).  of  theoretical  presented here corresponds  was t h e e x t r a c t i o n  analysis  it  the sexual  a preliminary  analysis  measures  Although  a model of  w i t h t h e one p r e s e n t e d b y Sachs  difference  male)  chambers.  study to present  of male r a t s ,  the  s t u d y has v a l i d a t e d  in the b i l e v e l  this  for  by  error.  I n summary, sexual  considerably  or  with  investigation, is  o f mounts  "gated" and  these aspects  of  s e x u a l behavior human c l i n i c a l  i s also reminiscent  l i t e r a t u r e between s e x u a l d e s i r e and  (e.g., DSM-IIIR; APA, may  of the d i s t i n c t i o n  1987).  a l l o w both e t h o l o g i c a l l y  of the s e x u a l behavior  i n the  arousal  Thus, the use of b i l e v e l chambers and  clinically  of male r a t s .  r e l e v a n t assessments  EXPERIMENT  II:  EFFECTS OF SYSTEMIC ADMINISTRATION OF DOPAMINE ANTAGONISTS ON ANTICIPATORY AND CONSUMMATORY ASPECTS OF SEXUAL BEHAVIOR I N THE MALE RAT  It  is widely believed  male s e x u a l m o t i v a t i o n & Zemlan,  and b e h a v i o r  DA a g o n i s t s  apomorphine can s t i m u l a t e m a l e s and c a n f a c i l i t a t e Conversely,  pimozide d i s r u p t  intromission  sexual desire  and d i s r u p t  males t h a t  display  intact,  aspects  a DA a n t a g o n i s t  Although  does n o t  inferences  sexual motivation  of  that  of  male r a t s  central  (Falaschi  behavior  effects  example,  typically  following  human in  male  and  initiation rate of  In  of  and h i t  rate  DA a n t a g o n i s t s  DA r e c e p t o r s  et  of  al., of  DA a n t a g o n i s t s ,  DA i n  the a d m i n i s t r a t i o n  are  because the of  the c a n be  some o f  with respect  in  1981).  male r a t s  i n c r e a s e d mount and i n t r o m i s s i o n  observed  in  and  the copulatory behavior  of  the  the  does n o t r e a d i l y c r o s s  made b y a s s e s s i n g t h e e f f e c t s  motivation,  the  about the normal r o l e  For  Crowley  i n human m a l e s .  copulatory  affect  and c o p u l a t o r y  are p a r a d o x i c a l .  in  s u c h as h a l o p e r i d o l  The e f f e c t s  the blockade  sexually active  1987;  and e j a c u l a t i o n  abolish  copulation.  barrier,  & Hull,  and a r o u s a l  and a r o u s a l  copulation  blood-brain  facilitate  As o u t l i n e d  sexual desire  t h e s e drugs d e l a y or  domperidone,  (Bitran  1988).  DA a n t a g o n i s t s  to r e f l e c t  DA s y s t e m s  s u c h as 1-DOPA, d - a m p h e t a m i n e ,  male r a t s ,  believed  central  1 9 8 1 ; Sachs & M e i s e l ,  Introduction,  rats.  that  to  these  sexual  latencies of  DA a n t a g o n i s t s  can  be  i n t e r p r e t e d as a d i s r u p t i o n whereas the decreased number  of i n t r o m i s s i o n s facilitation  before  (e.g.,  e j a c u l a t i o n can  Sachs & B a r f i e l d ,  e f f e c t that could and  by  However, t h e r e  number of  e x p l a i n both the  increased  intromissions  Although mount l a t e n c i e s may  intromission  before  activity,  female's l e v e l of s e x u a l  may  to s p e c i f y a r o l e of c e n t r a l DA  sexual  behavior based on the  consummatory measures of A more i n f o r m a t i v e sexual  motivation  receptor  e f f e c t s of DA  Thus, i t  systems i n male  antagonsits  on  copulation. way  to a s s e s s the r o l e of DA  on both a n t i c i p a t o r y and  measures of male s e x u a l  the  be  receptivity.  of male r a t s i s to e v a l u a t e  antagonists  latency  measure of  they can  confounded by the be m i s l e a d i n g  an  ejaculation.  be a more a p p r o p r i a t e  to i n i t i a t e c o p u l a t o r y  is  penile  i n t a c t male r a t s (Pehek et a l . , 1988),  decreased number of  motivation  i n t e r p r e t e d as a  1976).  evidence t h a t h a l o p e r i d o l decreases the erections displayed  be  behavior.  i n the  the e f f e c t s of  DA  consummatory  Thus, i n the second  experiment  of t h i s t h e s i s , the dose-response e f f e c t s of c e n t r a l l y - a c t i v e DA receptor  antagonists  copulatory antagonists  behavior  were examined on  l e v e l changing  i n s e x u a l l y a c t i v e male r a t s .  These  comprised s e v e r a l c l a s s e s , i n c l u d i n g the  n e u r o l e p t i c s h a l o p e r i d o l and  and  typical  pimozide, the a t y p i c a l n e u r o l e p t i c  clozapine,  the a n t i e m e t i c  agent metoclopramide, the D l - s e l e c t i v e  antagonist  SCH  the D 2 - s e l e c t i v e  sulpiride.  23390, and  atypical neuroleptic  78  Method S u b j e c t s and Surgery The male Long-Evans r a t s used i n Experiment II were purchased from C h a r l e s R i v e r Canada and housed as i n Experiment I.  The s t i m u l u s females used i n Experiment I were used i n  Experiment I I .  Sexual r e c e p t i v i t y was induced i n t h e females as  i n Experiment I . Drugs Haloperidol  (McNeil) was d i s s o l v e d  in distilled  few drops of d i l u t e g l a c i a l a c e t i c a c i d to o b t a i n of  0, 0.05, 0.1, 0.2, and 0.5 mg/ml.  were i n j e c t e d dissolved  concentrations  A l l doses of h a l o p e r i d o l  SC 1 hr b e f o r e t e s t i n g .  in distilled  water w i t h a  Pimozide  (McNeil) was  water c o n t a i n i n g 0.1 N HC1 and brought t o  pH 6 w i t h 0.01 N NaOH t o o b t a i n c o n c e n t r a t i o n s of 0, 0.1, 0.5, 1, and 5 mg/ml. testing.  A l l doses of pimozide were i n j e c t e d SC 4 hr b e f o r e  C l o z a p i n e (Sandoz) was d i s s o l v e d  in distilled  water  c o n t a i n i n g 0.1 N HC1 and brought t o pH 6 w i t h 0.01 N NaOH t o o b t a i n c o n c e n t r a t i o n s of 0, 0.1, 0.5, 1, and 5 mg/ml. of  c l o z a p i n e were i n j e c t e d  hydrochloride  SC 1 hr b e f o r e t e s t i n g .  (Sigma) was d i s s o l v e d  drops of g l a c i a l  in distilled  A l l doses  Metoclopramide  water with a few  a c e t i c a c i d t o o b t a i n c o n c e n t r a t i o n s of 0, 0.1,  0.5, 1, and 5 mg/ml.  A l l doses of metoclopramide were  SC 1 hr b e f o r e t e s t i n g . 23390 h y d r o c h l o r i d e  injected  The s e l e c t i v e DI r e c e p t o r a n t a g o n i s t SCH  ( S c h e r i n g Co) was d i s s o l v e d  in d i s t i l l e d  water t o o b t a i n c o n c e n t r a t i o n s of 0, 0.01, 0.05, 0.1, and 0.5 mg/ml.  A l l doses of SCH 23390 were i n j e c t e d SC 1 hr b e f o r e  79 testing.  The s e l e c t i v e  was d i s s o l v e d t o pH 6 w i t h 5,  in d i s t i l l e d  water  antagonist  containing  sulpiride  All  testing.  All  doses of  i n each d r u g  of  0,  brought  0.5,  1,  sulpiride  were i n j e c t e d  SC 1 h r  injected  in a constant  volume  d r u g s were  1 m l / k g body w e i g h t .  (Sigma)  0 . 1 N HC1 and  0 . 0 1 N NaOH t o o b t a i n c o n c e n t r a t i o n s  and 10 m g / m l .  before  D2 r e c e p t o r  The v e h i c l e  solution  s e r v e d as t h e  of  control  condition.  Apparatus The b i l e v e l i n Experiment Behavioral  of  These t e s t s  of  tests,  300 m a l e r a t s  the middle t h i r d  each male was p l a c e d of  level  f e m a l e was p l a c e d each mount,  of males t h a t  inclusion  into  displayed  Experimental  into  the dark one o f  I  for  (Page 5 9 ) .  cycle.  20 m i n .  During  these for  receptive  The o c c u r r e n c e  t h e same 11 m e a s u r e s  In addition,  the  percentage  intromissions,  and for  I.  Procedures  Following the  last  baseline  of  on a  males a c h i e v e d t h e c r i t e r i a  i n Experiment  II.  every  chambers  was r e c o r d e d  changes, mounts,  All  least  to Experiment  which a s e x u a l l y  which d e r i v e d  level  prior  the b i l e v e l  and e j a c u l a t i o n  was r e c o r d e d .  specified  of  t h e chamber  event recorder  i n Experiment  ejaculations  700 g ) w e r e g i v e n a t  and w e r e c o n d u c t e d one  changing a f t e r  intromission,  computerized analyzed  (450 t o  w e r e 25 m i n i n d u r a t i o n  a 5-min t e s t  used  Procedures  masculine copulatory behavior  4 days d u r i n g  I were  II.  Testing  A total 10 t e s t s  t e s t i n g chambers used i n E x p e r i m e n t  screening t e s t ,  experimental  80 r a t s were a s s i g n e d group).  Within  randomly to one  of s i x drug groups  each group, 10 r a t s were a s s i g n e d  of the f i v e doses of the drug and  50/  randomly to  r e c e i v e d the dose or  c o n t r o l s o l u t i o n i n a randomized order at 4-day Experimental  (n =  one  the  intervals.  t e s t s began 4 days a f t e r the l a s t s c r e e n i n g t e s t  and  were conducted i d e n t i c a l l y to i t . Statistical The  Analyses  e f f e c t s of d i f f e r e n t doses of each drug on the  measures of s e x u a l behavior d a t a of those behavior  11  were compared s t a t i s t i c a l l y u s i n g  r a t s i n each group t h a t d i s p l a y e d the  the  sexual  under a n a l y s i s ; no a r b i t r a r y s c o r e s were a s s i g n e d .  Where a p p r o p r i a t e , the s i g n i f i c a n c e of the d i f f e r e n c e s i n the p r o p o r t i o n of r a t s i n each drug dose c o n d i t i o n t h a t d i s p l a y e d mounts, i n t r o m i s s i o n s , or e j a c u l a t i o n s was square t e s t s , p_<.05, t w o - t a i l e d . behavior way  The  assessed  using c h i -  11 measures of  sexual  w i t h i n each drug group were s u b j e c t e d to m u l t i p l e one-  analyses  of c o v a r i a n c e  (ANCOVA) a c r o s s d i f f e r e n t doses,  with  the c o n t r o l measures s e r v i n g as the c o v a r i a t e s f o r the r e s p e c t i v e drug dose measures. t h e i r own  T h i s procedure allowed  c o n t r o l s and  provided  animals  to be used  a t r u e index of change f o r the  e f f e c t s of each drug dose on each measure of s e x u a l Because a l l of the measures of s e x u a l behavior changing were found  method  behavior.  except  to be r e l a t e d s t a t i s t i c a l l y  the ANCOVAs run on these measures i n the p r e s e n t corrected  The  level  i n Experiment I, a n a l y s i s were  f o r e l e v a t e d experiment-wise e r r o r u s i n g the  ( O v e r a l l & Rhodes, 1987).  as  Bonferroni  adjusted Bonferroni  alpha  81 for  each ANCOVA was .005.  For each s i g n i f i c a n t ANCOVA, post-hoc  comparisons of the e f f e c t s of each dose were made u s i n g  the Tukey  method.  Results Haloper i d o l The h i g h e s t  dose of h a l o p e r i d o l  decreased the p r o p o r t i o n  (0.5 mg/kg) s i g n i f i c a n t l y  of r a t s t h a t d i s p l a y e d  l e v e l changes, X  1  (1, N=20) = 5.95, p_<.025; mounts, X ( l , N=20) = 7.91, p_<.005; l  intromissions,  X ( 1 , N=20) = 7.91, p_<.005; and e j a c u l a t i o n s , X*" L  (1, N=20) = 10.21, p_<.005 ( F i g u r e  3).  These r a t s appeared  sedated and d i d not d i s p l a y much i n t e r e s t i n the r e c e p t i v e females.  Because h a l o p e r i d o l has s e d a t i v e  e f f e c t s a t high  data from t h e r a t s i n t h i s group were not s u b j e c t e d statistical  analysis.  further to  None of the other doses of h a l o p e r i d o l  s i g n i f i c a n t l y decreased the p r o p o r t i o n l e v e l changes, mounts, i n t r o m i s s i o n s , Consistent  doses,  of r a t s t h a t  displayed  or e j a c u l a t i o n s .  with e a r l i e r d a t a , the ANCOVA  detected  s i g n i f i c a n t e f f e c t s of h a l o p e r i d o l on the LC, F(3,35)=29.91, p_<. 00001; the I L , F( 3, 35 ) =21. 05, p_<.0001; the NI, F( 3, 35 ) =8 . 26, p_<.0004; and the NE, F ( 3, 35) =8. 89, p_<.0003 ANCOVA a l s o d e t e c t e d  (Figure  4).  The  an e f f e c t of h a l o p e r i d o l on the ML,  F(3,35)=3.99,  p_<.01; the PEI, F( 3,34) =2 .93, p_<.04; the I I I ,  F(3,34)=3.51,  p_<.03; and the IR, F( 3, 35) =3. 72, p_<.02; however,  these e f f e c t s d i d not reach the l e v e l of s i g n i f i c a n c e r e q u i r e d the  Bonferroni  correction.  Haloperidol  had no s i g n i f i c a n t  by  82  Figure  3.  Percentage of r a t s d i s p l a y i n g l e v e l changes, mounts, i n t r o m i s s i o n s , and e j a c u l a t i o n s f o l l o w i n g t r e a t m e n t w i t h d i f f e r e n t doses of h a l o p e r i d o l i n E x p e r i m e n t I I . * * p_<.05, * p_<.01, f r o m c o n t r o l v a l u e s .  DOSE OF HALOPERIDOL ( m g / k g )  84  Figure  4.  E f f e c t o f d i f f e r e n t d o s e s o f h a l o p e r i d o l on t h e 9 p r i m a r y m e a s u r e s o f male s e x u a l b e h a v i o r o b s e r v e d Experiment I I . V a l u e s a r e means a d j u s t e d f o r t h e c o v a r i a t e + SE. * * p < . 0 5 , * p_<.01 f r o m c o n t r o l v a l u e s . /  in  MEAN NUMBER i  i  i  i  i  i  i — i  ' • • ' < •  i i  •  MEAN NUMBER  (sec)  MEAN LATENCY  K t s s s i i s i •  •  '  •  •  '  •  •  »  •  •  •  •  •  •  •  •  •  o  MEAN LATENCY  • _ i  MEAN NUMBER  MEAN LATENCY 8 B 8  (sec) fi  ttsssiitss •  »  • *  •  i >  MEAN LATENCY 0  (eec)  8  6  8  8  8  8  8  (sec) 8  8  86 overall  effect  comparisons higher  on o t h e r  of  doses,  measures o f  the e f f e c t  The e f f e c t  significantly contrast,  of  lower  of the c o n t r o l  the  than the e f f e c t  solution  of  the  and t h e  lower  two  lower  also  0.1-mg/kg dose.  o n l y t h e 0 . 2 - m g / k g dose s i g n i f i c a n t l y  and t h e  the  r e d u c e d LC  0 . 2 - m g / k g d o s e on LC was  and r e d u c e d t h e N I and NE compared t o solution  Post-hoc  each dose r e v e a l e d t h a t  0 . 1 and 0 . 2 m g / k g , s i g n i f i c a n t l y  compared t o t h e e f f e c t s dose.  of  sexual behavior.  increased  the e f f e c t s  of  the  In the  IL  control  doses.  Pimozide The e f f e c t s haloperidol.  of  p i m o z i d e were s t r i k i n g l y  The h i g h e s t d o s e ,  decreased the p r o p o r t i o n (1,  N=20)=4.27,  intromissions, N=20)=16.20, that  X*(l,  p_<.005  received  interest  this  rats  mounts,  that  (Figure  X  females.  proportion  did of  intromissions  not  rats  and e j a c u l a t i o n s , the  Data from the r a t s  engaged i n s e x u a l b e h a v i o r analysis.  reach s t a t i s t i c a l that  was n o t  displated  affected  by t h e  p_< . 0 0 0 0 2 ;  the  rats  that  lower doses of  IL,  in  z  l  effects  ;  rats much  this  subjected of  ejaculated, The  changes, mounts,  overall  X  X (l  1 . 0 - m g / k g dose  significance.  level  The ANCOVA d e t e c t e d s i g n i f i c a n t on L C , F ( 3 , 3 5 ) = 1 5 . 1 2 ,  were n o t  Although the of  of  p_<.005;  d o s e a p p e a r e d s e d a t e d and d i d n o t d i s p l a y  to s t a t i s t i c a l  effect  those  changes,  As w i t h h a l o p e r i d o l ,  pimozide also decreased the p r o p o r t i o n this  level  X ( 1 , N=20)=7.91,  5).  to  significantly  displayed  N = 2 0 ) = 1 0 . 2 1 , p_<.005;  in the receptive  dose g r o u p t h a t further  p_<.05;  of  5.0 mg/kg,  similar  and  pimozide. of  pimozide  F ( 3 , 35) =6 . 79 , p_<.001;  the  87  Figure  5.  Percentage of r a t s d i s p l a y i n g l e v e l changes, mounts, i n t r o m i s s i o n s , and e j a c u l a t i o n s f o l l o w i n g treatment with d i f f e r e n t doses of pimozide i n Experiment I I . * * p_<.05, * p_<.01, from c o n t r o l v a l u e s .  DOSE OF PIMOZIDE ( m g / k g )  89  F i g u r e 6.  E f f e c t of d i f f e r e n t doses of pimozide on the 9 p r i m a r y measures of male s e x u a l b e h a v i o r observed i n Experiment I I . Values a r e means a d j u s t e d f o r the c o v a r i a t e + SE. * * p_<.05, * p_<.01, from c o n t r o l v a l u e s .  MEAN NUMBER O  M  «  «  » 1  S I  S I  I  I  S I I  MEAN LATENCY » I I  I  0 1  •  ft  8 i  i  i  8 i—i—i  8 i  MEAN NUMBER  (soc) 8 •  i  •  8 •  O I  M i  •  i  »  *  i  » •  » i  S i  i  S i  i  i  « •  5  *  8 II  ** MEAN NUMBER •  •  •  MEAN LATENCY •  •  •  MEAN NUMBER — i — i  1  1  •  •  J  8 i  i  B i  i  B i  MEAN LATENCY •  •  i  I  fi  MEAN LATENCY  (sec) »  § »  (ssc) I  •  4  8 I  I  8 I  I  8 I  1  8 1  •  MEAN LATENCY 8  8  8  8  (ssc) 8 •  •  8 •  (ssc) 8  8  91 PEI,  F(3,30)=5.88,  F(3,35)=7.78, 6).  p_<.003;  p_<.0006;  t h e N I , F ( 3 , 35) =7 . 6 9 , p_<.0007;  and t h e  The ANCOVA a l s o d e t e c t e d  F(3,30)=4.89, significance no e f f e c t  p_<.007,  an e f f e c t  this  of  doses of  control  effect  measures o f  the e f f e c t  of  of  sexual  v a l u e whereas o n l y t h e IL,  p_<.004  pimozide  d i d not  on t h e  reach the  correction.  behavior.  (Figure  1.0  P E I , and I I I ,  of  Pimozide  had  Post-hoc the  r e d u c e d t h e NE f r o m mg/kg dose  EL,  level  0.5  r e d u c e d LC f r o m t h e c o n t r o l  pimozide s i g n i f i c a n t l y  increased the  5.77,  each dose r e v e a l e d t h a t  1.0-mg/kg doses s i g n i f i c a n t l y All  F(3,30)=  r e q u i r e d by t h e B o n f e r r o n i  on o t h e r  comparisons  but  III,  t h e NE,  and  value.  the  significantly  and d e c r e a s e d t h e N I  from  control  values. Clozapine None o f clozapine  the r a t s  initiated  treated with the  copulatory  d i s p l a y e d reduced r a t e s mg/kg dose a l s o that  p_<.005, level  p_<.005;  whereas a l l  changing.  clozapine highest  of  moved f r e e l y  changing  these r a t s  investigation  percentage  of  10  The of  rats  1.0rats  2  reduced r a t e s  sedated than the r a t s or p i m o z i d e .  Most o f  females.  in copulatory  of  doses  treated with  displayed  the receptive  engaged  the  intromissions,  t r e a t e d w i t h t h e two h i g h e s t  of  of  X - ( 1 , N = 2 0 ) = 10 . 2 1 ,  displayed  a b o u t t h e chambers and a l l  anogenital  7).  decreased the p r o p o r t i o n  and e j a c u l a t i o n s ,  haloperidol  that  (Figure  z  The r a t s  rats  whereas 9 of  X ( 1 , N = 2 0 ) = 7 . 9 1 , p_< . 0 0 5 ;  appeared l e s s  doses of  behavior,  level  significantly  d i s p l a y e d mounts,  (1,N=20)=7.91,  of  5 . 0 - m g / k g dose  of  the  these  rats  periods  of  Because  behavior  was  the  X  z  92  Figure  7.  Percentage of r a t s d i s p l a y i n g l e v e l changes, mounts, i n t r o m i s s i o n s , and e j a c u l a t i o n s f o l l o w i n g treatment with d i f f e r e n t doses of c l o z a p i n e i n Experiment I I . * * p_<.05, * p_<.01, from c o n t r o l v a l u e s .  DOSE OF CLOZAPINE ( m g / k g )  94  Figure  8.  E f f e c t o f d i f f e r e n t d o s e s o f c l o z a p i n e on t h e 9 p r i m a r y measures o f male s e x u a l b e h a v i o r o b s e r v e d Experiment I I . V a l u e s a r e means a d j u s t e d f o r t h e c o v a r i a t e + SE. * p_<.05,  * p_<.01,  from c o n t r o l  values.  in  MEAN LATENCY  MEAN NUMBER  MEAN NUMBER  (sac)  _i i i • • • i i i i i i i • • •  z  o  O  o  CO  m  MEAN LATENCY 8 1 8  MEAN NUMBER  o ~n o  (sac) 8  MEAN LATENCY 8  8  8  8  (sec) 8  8  r~ O NI >  o  2  m uQ  MEAN NUMBER  MEAN LATENCY 1 8 8  7T  2 m  (sec) 8  MEAN LATENCY 8  ft  8  8  (sec) 8  8  96 significantly copulatory  displayed  analysis  level level  of  In rats  that  F(4,44)=22.04, of  d i s p l a y e d measures o f  a significant  overall  p_<. 0 0 0 0 1 ( F i g u r e  of  to  rats  different  g r o u p s were  these e f f e c t s  d i d not  the Bonferroni  in  subjected  reach the  of  Post-hoc  rates  clozapine  p_<.03;  the  significance  of  comparisons  on L C ,  on of  1.0,  and 5 . 0 - m g / k g  the other  of  an  IL,  although required  by  other the  LC w e r e s i g n i f i c a n t l y  5 . 0 - m g / k g dose r e d u c e d r a t e s  from those of  the  The ANCOVA a l s o d e t e c t e d  level  v a l u e by t h e 0 . 5 ,  Treatment w i t h the  of  C l o z a p i n e had no e f f e c t  behavior.  each dose r e v e a l e d t h a t  from the c o n t r o l  effect  behavior,  and t h e NE, F( 2 , 25) = 5 . 0 0 , p_<.01,  correction.  sexual  8).  sexual  on t h e ML, F( 2 , 2 6 ) = 3 . 9 8 ,  p_<.03;  significantly  of  further  because t h e p r o p o r t i o n  c h a n g i n g was n o t s i g n i f i c a n t l y  F(2,26)=3.87,  of  were n o t s u b j e c t e d  changing data from a l l  clozapine  measures o f  However,  t h e measures  covariance.  ANCOVA d e t e c t e d  effect  from these r a t s  analysis.  these groups, to  i n t h e s e two dose g r o u p s ,  behavior  statistical that  lower  effect reduced  doses.  LC  doses.  Metoclopramide None o f of  rats  t h e doses of m e t o c l o p r a m i d e decreased t h e  that displayed  ejaculations.  of  9);  however,  significance  measures of  changing, mounts,  The ANCOVA d e t e c t e d an e f f e c t  the N I , F(4,44)=3.22, (Figure  level  p_<.02; neither  and t h e of  III,  sexual  behavior  were a f f e c t e d  intromissions,  or  of metoclopramide  on  F( 4 , 44 ) =3 . 2 3 , p_<.02  these e f f e c t s  r e q u i r e d by t h e B o n f e r r o n i  proportion  reached the  correction. significantly.  No  level other  97  F i g u r e 9.  E f f e c t of d i f f e r e n t doses of metoclopramide on the 9 primary measures of male s e x u a l behavior observed i n Experiment I I . Values a r e means a d j u s t e d f o r the c o v a r i a t e + SE. * * p_<.05, * p_<.01, from c o n t r o l v a l u e s .  MEAN NUMBER  MEAN LATENCY (sec)_  MEAN NUMBER o •  •  •  I  I  I  .  ,  •  1  MEAN LATENCY (sec) i B B 8 •  •  1  1  1  1  •  •  MEAN NUMBER  MEAN LATENCY o •  8  *  8  8  (sec) 8  i  i — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1 — 1  99 SCH 23390 A l t h o u g h SCH 23390 d e c r e a s e d t h e p r o p o r t i o n displayed  level  these e f f e c t s  changes, mounts,  d i d not  The ANCOVA d e t e c t e d  reach s t a t i s t i c a l  significant  L C , F ( 4 , 4 4 ) = 5 5 . 0 1 , p_< . 0 0 0 0 1 ; IL,  intromissions,  of and  significance  overall  effects  of  11).  (Figure  The ANCOVA a l s o d e t e c t e d  and t h e  d i d not  III,  reach the  Bonferroini  an o v e r a l l  SCH 23390  of  correction.  significance  Despite the  t h e ANCOVA d i d n o t d e t e c t  t h e s e or  other  the e f f e c t  significantly solution.  measures o f  required  fact  of  overall  sexual  that  all  behavior.  doses of  significantly  different  highest  0.5 mg/kg, s i g n i f i c a n t l y  dose,  all  by  of  effects  the  variation  in  effects  for  the  Post-hoc  comparisons  doses of  SCH 23390  of  the  control  SCH 23390 on LC w e r e  f r o m one a n o t h e r .  PEI compared t o t h e e f f e c t s  SCH  SCH 23390  r e d u c e d LC c o m p a r e d t o t h e e f f e c t of  of  these  significant  each dose r e v e a l e d t h a t  The e f f e c t  the  p_<.0007  effect  however,  i n c r e a s e d t h e LCL and p r o d u c e d a l a r g e d e g r e e o f EL,  on  t h e NE, F( 4 , 39 ) =2 . 9 5 ,  F( 4 , 39 ) =2 . 9 2 , p_<.03;  level  10).  t h e ML, F ( 4 , 41) =12 . 6 2 , p_<.0001;  23390 on t h e N I , F( 4 , 41) =3 . 2 7 , p_<.02; p_<.03;  that  ejaculations,  F ( 4 , 4 1 ) = 1 3 . 5 1 , p_<.0001; and t h e P E I , F ( 4 , 39 ) =6 . 4 3 ,  (Figure  of  rats  only  the  i n c r e a s e d t h e ML, I L ,  and  the c o n t r o l  In contrast,  also  solution  and t h e  lower  doses. Sulpiride None o f rats  that  t h e doses of  displayed  ejaculations.  level  sulpiride changes,  The ANCOVA d e t e c t e d  decreased the p r o p o r t i o n mounts,  intromissions,  a significant  overall  of  or effect  100  Figure  10.  Percentage of r a t s d i s p l a y i n g l e v e l changes, mounts, i n t r o m i s s i o n s , and e j a c u l a t i o n s f o l l o w i n g t r e a t m e n t w i t h d i f f e r e n t d o s e s o f SCH 23390 i n E x p e r i m e n t I I . * * p_<.05, * p_<.01, f r o m c o n t r o l v a l u e s .  LEVEL CHANGES  DOSE OF SCH 2 3 3 9 0  MOUNTS  (mg/kg)  102  Figure  11.  E f f e c t o f d i f f e r e n t d o s e s o f SCH 23390 on t h e 9 p r i m a r y measures of male s e x u a l b e h a v i o r o b s e r v e d Experiment I I . V a l u e s a r e means a d j u s t e d f o r t h e c o v a r i a t e + SE. * * p_<.05 * p_<.01, f r o m c o n t r o l v a l u e s . /  in  MEAN LATENCY (sec^  MEAN NUMBER  MEAN NUMBER  i i i i i i i i—i—i—i i • • • •  MEAN NUMBER j  i i i i i i i—i i i i i i i i  z  MEAN NUMBER -  •*  1  M  1 1  M  1  *  1  L J  i  i  i  •  •  •  •  •  •  i  i  i  i  i  i  i  i  i  i  i  i  i  104  F i g u r e 12.  E f f e c t of d i f f e r e n t doses of s u l p i r i d e on the 9 primary measures of male s e x u a l b e h a v i o r observed i n Experiment I I . Values a r e means a d j u s t e d f o r the c o v a r i a t e + SE. * * p_<.05, * p_<.01 from c o n t r o l v a l u e s . /  r /  MEAN NUMBER .  .  s  s  MEAN LATENCY (sec)  :  s  0  .  ?  0  MEAN NUMBER :  '  , • 17 1  '  ^  1  7  1  8  6  8  8  8  8  6  8  8  MEAN NUMBER  o - * . - s s : s 5 8  MEAN LATENCY (sac) 1  1  8  S  B  I  1 1 1 1 1 1 • • 1  MEAN LATENCY (sec) .  8  6  8  8  8  8  6  8  8  1—1—1—J—1 1 1 1 1 1 1 1 • 1 • 1 • 1 1  106 of  sulpiride  on LC, F( 4 , 44 ) =6 . 5 6 , p_<.0005.  d e t e c t e d an o v e r a l l p_<.03,  this  effect  effect  of  d i d not reach the  r e q u i r e d by t h e B o n f e r r o n i measures of sulpiride  12).  LC c o m p a r e d t o  the  the e f f e c t s  level  of  IL,  F(4,44)=2.92,  significance  None o f  were a f f e c t e d  Post-hoc  each dose r e v e a l e d t h a t  on t h e  correction.  sexual behavior  (Figure  sulpiride  A l t h o u g h t h e ANCOVA  the  other  significantly  comparisons  of  by  the e f f e c t  10-mg/kg dose s i g n i f i c a n t l y of  the c o n t r o l  solution  of  reduced  and t h e  lower  doses.  Discussion Experiment antagonists intact, it  confirmed  differentially  sexually active  extends these  anticipatory typical  II  neuroleptics  number o f  level  changes  intromission  latencies,  5-min p e r i o d  and t h e D 2 - s e l e c t i v e  b o t h d e c r e a s e d t h e number o f latencies,  intromission  latencies  that  female,  1989),  the a t y p i c a l  atypical  level  the  the  of  mounts  abolished neuroleptic sulpiride  c h a n g e s and i n c r e a s e d  was o f m a r g i n a l  The  the  preceded  neuroleptic  although the e f f e c t  and  of  increased  these drugs  of  chambers.  and d e c r e a s e d t h e p r o p o r t i o n  Similarly,  intromission  behavior  a form  in bilevel  DA  and p i m o z i d e d e c r e a s e d  High doses of  behavior.  that  & Phillips,  changing,  a sexually receptive  intromission.  clozapine  (Pfaus  observed  in the  finding  the copulatory  level  haloperidol  of  copulatory  to  behavior  introduction  with  affect  male r a t s  findings  sexual  the previous  of s u l p i r i d e  significance.  the on  However,  107 neither  drug a f f e c t e d  High doses of Dl-selective changes,  the proportion  clozapine antagonist  also  mounts w i t h  intromission  These r e s u l t s neuroleptic  initiate  confirm previous  drugs d e l a y or  1989)  differentially  abolish the  Phillips,  1989).  following  or p i m o z i d e  of  A l t h o u g h moderate doses of  experiments, statistical  only the e f f e c t significance  1984; Pfaus &  intromission 1984; Pfaus &  several  with previous  of  First,  have  been  haloperidol  Mcintosh & B a r f i e l d ,  in the  pimozide  results  reports.  interval  haloperidol  interval  atypical  DA a n t a g o n i s t  findings,  1984a,b;  level  copulation  w i t h moderate doses of  & Larsson,  increased the postejaculatory  and  of  al.,  of  in the p o s t e j a c u l a t o r y  treatment  (Ahlenius  Initiation  mounts w i t h  these  were i n c o n s i s t e n t  increases  typical  et  of  intromissions.  1984a; Mcintosh & B a r f i e l d ,  Despite the consistency II  that  t h e s e two c l a s s e s  r e d u c e t h e number o f  & Larsson,  substantial  reports  and  Finally,  t h e number o f  m o u n t s and  1984; N a p o l i - F a r r i s  and t h a t  (Ahlenius  in Experiment  level  latencies,  intromission.  but d i d not a f f e c t  latency to  (Mcintosh & B a r f i e l d , Phillips,  o f mounts w i t h  of  The  agent metoclopramide decreased the p r o p o r t i o n  changes or t h e  However,  behavior.  i n c r e a s e d b o t h t h e mount and i n t r o m i s s i o n  the antiemetic  1984).  abolished copulatory  intromission.  SCH 23390 d e c r e a s e d t h e number  decreased the p r o p o r t i o n  reported  o f mounts w i t h  and  pimozide  present  reached the  r e q u i r e d by t h e B o n f e r r o n i  i n our  previous  study,  the e f f e c t  postejaculatory  interval  was o f  marginal  of  level  of  correction.  pimozide  significance  on  the  (Pfaus &  108 Phillips,  1989).  Similarly,  decrease the e j a c u l a t i o n Although the decrease  in the present  previous  study  measure  (Pfaus  sulpiride however,  to  find  & Phillips,  of  experiments  of  behavior,  a conservative  method)  error  o c c u r s when t h e s t a t i s t i c a l  measures It  is is  assessed  sulpiride,  changes a t doses t h a t level  copulatory  did not with  sensitive  to the d i s r u p t i v e  the  (the  experiment-wise  haloperidol,  This  of  related  pimozide,  latency to  effect  of  DA a n t a g o n i s t s  latencies is  that  sexual  level  affect level is  more  than  motivation  or t h e p r o p o r t i o n  consistent  of  initiate  sexual m o t i v a t i o n ,  measures o f  This  did not  indicates  anticipatory  copulatory-based  intromission).  the  few e x c e p t i o n s ,  mount and i n t r o m i s s i o n  mounts w i t h  including  present  significance  increase  behavior.  as a measure o f  (e.g.,  from a  and SCH 23390 d e c r e a s e d t h e number  changing,  traditional,  marginal  procedure  the elevated  to note t h a t  c h a n g e s and t h a t ,  measures o f  latency;  independently.  interesting  clozapine,  for  this  different  and t h e use i n t h e statistical  our  study,  procedures,  animals w i t h  Bonferroni that  to correct  was o f  on  may have r e s u l t e d  methodological  t e s t i n g chambers,  sexual  pimozide  intromission  effect  These i n c o n s i s t e n c i e s  use o f d i f f e r e n t  of  by  significant,  I n our p r e v i o u s  study t h i s  combination of d i f f e r e n t  baselines  1989).  1984).  l a t e n c y produced  any e f f e c t  increased the  in the present  to  (Mcintosh & B a r f i e l d ,  s t u d y was m a r g i n a l l y  significantly  significance.  latency  has been r e p o r t e d  in the e j a c u l a t i o n  pimozide  failed  pimozide  of  w i t h data from  the  109 f e e d i n g and a v o i d a n c e  literatures  preparatory behaviors,  suggesting that  s u c h as i n s t r u m e n t a l  anticipatory  responding,  sensitive  t h a n consummatory b e h a v i o r s ,  s u c h as f e e d i n g  avoiding,  to the d i s r u p t i v e  DA a n t a g o n i s t s  1989; al.,  Blackburn et a l . , 1979).  The f a c t  effects  1987; F i b i g e r  that  initiation  of  finding  in Experiment  However,  the present  the  influence  produce r e l a t i v e (e.g.,  1 that results  anticipatory  low doses o f  support  literatures  that  ataxia.  Clearly,  aspects  ejaculations),  and mount c o u n t  mounts w i t h  intromission)  were a f f e c t e d  antagonists  t h a t d i d not d i s r u p t  behavior  eliminate  central  DA s y s t e m s a r e  it  other  altogether.  involved  and c o n s u m m a t o r y a s p e c t s  Previous mesolimbic  Lane & B l a h a ,  independent. made  of c o p u l a t o r y (e.g.,  in  do  not that  rate  the  t h e number  aspects It  of  of  copulatory  would appear  that  anticipatory/preparatory  of masculine sexual behavior aspects  a r e more  in the  rat,  sensitive  b y DA a n t a g o n i s t s . studies  have s u g g e s t e d a d i f f e r e n t i a l  and m e s o s t r i a t a l  extrapyramidal  the  b y d o s e s o f DA  in both  although the a n t i c i p a t o r y / p r e p a r a t o r y to disruption  to  DA a n t a g o n i s t s  (e.g.,  et  sexual  assertions  initiation  latencies),  or  (Blackburn,  DA a n t a g o n i s t s  t h e s e measures a r e do n o t  or  consummatory r e s p o n d i n g except a t doses  t h e number o f  intromission  with  more  1 9 7 4 ; Tombaugh  c o p u l a t i o n a l s o adds s u p p o r t  f e e d i n g and a v o i d a n c e  generally  et a l . ,  a measure o f  m o t i v a t i o n c a n be d i s s o c i a t e d from the  of  are  or  effects  of  DA t e r m i n a l s  DA a n t a g o n i s t s  1 9 8 6 ; W h i t e & Wang, 1 9 8 3 ) .  role  of  in the a n t i p s y c h o t i c (Chiodo & Bunney, The  systemic  and  1984;  110 administration  of  nonselectively  i n mesolimbic  Blaha,  In contrast,  1986).  clozapine  haloperidol  and s u l p i r i d e  mesolimbic  terminals,  metoclopramide  pimozide,  clozapine,  1986).  c h a n g e s and i n c r e a s e d t h e  administered mesolimbic, involved  initiation  of  copulation  The r e s u l t s relatively similar  i n male  behavior.  II  also  affinity effects  for that  and p i m o z i d e ,  level  whereas Although  it  was  t h e DA  suggest  that may be  sexual motivation  indicate  that  and  the  the  D I and D2 r e c e p t o r s and i n i t i a t i o n  sulpiride  of  has male  antagonist  SCH 23390  d e c r e a s e d t h e number  intromission  SCH 23390 a l s o d e c r e a s e d t h e number o f Haloperidol  of  systemically  Both the D l - s e l e c t i v e  c h a n g e s and i n c r e a s e d t h e  haloperidol,  rats.  antagonism of  antagonist  II,  DA t e r m i n a l s  anticipatory  on t h e a n t i c i p a t i o n  and t h e D 2 - s e l e c t i v e level  these r e s u l t s  of Experiment  selective  effects  copulatory  of  in  to determine of  both  mesostriatal  latencies,  experiment  than m e s o s t r i a t a l ,  in the d i s p l a y  of  d e c r e a s e d t h e number  in the e f f e c t s  DA a n t a g o n i s t s ,  (Lane &  of  in  on t h e s e m e a s u r e s .  the present  involved  rather  selectively  In Experiment  intromission  had no e f f e c t  regions  terminals  selectively  and s u l p i r i d e  DA r e l e a s e  administration  DA r e l e a s e  DA r e l e a s e  (Lane & B l a h a ,  terminal  the systemic  affects  terminals  not the purpose of  and m e s o s t r i a t a l  whereas t h e a d m i n i s t r a t i o n  affects  metoclopramide  and p i m o z i d e a f f e c t s  latencies,  mounts w i t h  of  although  intromission.  b o t h of which possess a g r e a t e r  D2 t h a n D I r e c e p t o r s were v i r t u a l l y  (Tamminga & G e r l a c h ,  identical  t o SCH 2 3 3 9 0 .  1987),  These  had  Ill effects  are c o n s i s t e n t  and D 2 - s e l e c t i v e inhibit  neurons  with reports  compounds.  i n t h e n u c l e u s accumbens,  by t h e c o a d m i n i s t r a t i o n  Chase,  In addition,  Perregaard, activation  1 9 8 7 ; Weick & W a l t e r s ,  1986),  (Melis,  Argiolas,  reports  of  opposite  & Gessa,  of  selective  i n the s t r i a t u m  Spampinato,  Glowinski,  oral  stereotypies  contralateral  (Asin & Montana,  Carlson,  to  (Arnt,  1986),  1986).  act Hyttel, &  behavioral  turning  behavior  tract  lesions  (Robertson &  However,  DA r e c e p t o r  erection there  agonists  (Fage & S c a t t o n , 1984),  & Nishi,  (Johansen,  Levin,  1986), Gunne,  following  syndrome  are  also  including on GABA and  1986;  Girault,  on t h e a b i l i t y  or d e p o l a r i z a t i o n s  in rats  enhanced  1986),  Higashi,  rotation  and  1 9 8 7 ; W h i t e & Wang,  D I and D2 r e c e p t o r s ,  & Besson,  induce h y p e r p o l a r i z a t i o n s (Uchimura,  of  agonists  is  Bergstrom,  stereotypies  of  Dl-  (Carlson,  have been r e p o r t e d  1987).  actions  of  pallidus,  agonists  and t h e y a w n i n g and p e n i l e  opposite  effects  mesostriatal  ACh r e l e a s e  neurons  of  (Jackson & Hashizume,  Robertson,  globus  1987; Mashurano & W a d d i n g t o n ,  unilateral  D2-selective  1988; W a l t e r s ,  in the d i s p l a y  actions  and s u c h i n h i b i t i o n  Dl-selective  D I and D2 r e c e p t o r s  synergistically  following  of  Demo, & W a l t e r s ,  & Braun,  synergistic  For example,  s u b s t a n t i a n i g r a pars r e t i c u l a t a ,  Bergstrom,  of  of  nucleus  DA t o  accumbens  and on t h e d i s p l a y & Ellison)  intranigral  of  and infusions  1988).  The d i s r u p t i v e  effects  23390 and t h e D 2 - s e l e c t i v e and t h e . i n t r o m i s s i o n  of  the D l - s e l e c t i v e  antagonist  latencies  sulpiride  are also  antagonist on l e v e l  inconsistent  with  SCH  changing a  112 recent  report  by H u l l  the D2-selective intromission with  latencies  coadministration  receptor clearly  of  intromissions  following  those drugs  antagonist  actions  D2 t o  in the r e g u l a t i o n  masculine  sexual  behavior  terminal not.  t h e MPOA.  of  in the r a t ,  The r e s u l t s  of  mounts  certain it  is  exists  of Experiment  II  in other  suggest  as t h e d o s e s used were v e r y  t o be e x a m i n e d b e f o r e a g e n e r a l behavior  Finally, neuroleptics Gerlach,  it  anticholinergic  sites  that  to affect  role  of  may should  low.  raclopride,  D2 r e c e p t o r s  many t y p i c a l  5 - H T 2 , c < l , and H I r e c e p t o r s  and some a t y p i c a l activity  (Snyder  neuroleptic certain  it  in  a  DA  experiment  e.g.,  an  The need  male  hypothesized.  s h o u l d be n o t e d t h a t  bind to  1987),  conceivable  c a n be  in this  antagonists,  suggest  whether  cautiously,  sexual  and  of  be i n t e r p r e t e d  D2-selective  sulpiride  aspects  not clear  types  in  i n t h e MPOA i s  of  other  results  o f D I and D2 r e c e p t o r s  the e f f e c t s  of  D2  the  However,  effects  The  effective  selective  stimulation  among t h e s e r e c e p t o r  regions.  mounts  Although those r e s u l t s  factor  relation  of  study,  on t h e d i s p l a y  DI r e c e p t o r  and  and  s t u d y was more  in that  the s t i m u l a t i o n  important  similar  into  Although a r e l a t i v e l y  was n o t a s s e s s e d  that  of  infusion  in that  i n t h e male r a t .  the r a t i o  i n w h i c h b o t h SCH 23390  and d e c r e a s e d t h e p r o p o r t i o n  drug alone.  indicate  (1990)  LY 163502 i n c r e a s e d mount  in rats  t h e MPOA has o p p o s i t e  that  al.  agonist  intromission  than e i t h e r  et  neuroleptics et a l . ,  1974).  drugs could act  aspects  of  at  and  atypical  (Tamminga &  also It  possess is  thus  nondopaminergic  masculine sexual  behavior.  113 This  tentative  relatively selective  hypothesis  s e l e c t i v e oil  is  antagonist  5-HT2 a n t a g o n i s t  intromission & Gorzalka,  latencies 1985).  s u p p o r t e d by e v i d e n c e prazosin  plrenperone  (Clark,  Smith,  In addition,  both  SCH 2 3 3 9 0 , and m e t o c l o p r a m i d e ,  number  mounts w i t h  However, masculine  the  fact  copulatory  work by a s i n g l e considerable behavior  behavior  exists  does n o t  the 1985).  influence  on  necessarily  mean t h a t  they  receptor  attenuate  Mendelson  haloperidol,  also decreases  It  in the c o n t r o l  by e x a m i n i n g whether  can s e l e c t i v e l y  like  1985;  and  a similar  mechanism.  b y monoamines o r t h e i r  relatively  (Mendelson & G o r z a l k a ,  these drugs e x e r t  transmitter  overlap  c o u l d be t e s t e d agonists  that  the  i n c r e a s e mount  pirenperone,  intromission  the  & Davidson,  pimozide, of  or  that  is  possible  of masculine  subtypes.  specific  the e f f e c t s  This  monoamine of  that sexual idea receptor  DA a n t a g o n i s t s .  114 EXPERIMENT I I I : EFFECTS OF CENTRAL ADMINISTRATION  OF HALOPERIDOL  ON ANTICIPATORY AND CONSUMMATORY ASPECTS OF SEXUAL BEHAVIOR IN THE MALE RAT  The receptor  systemic a d m i n i s t r a t i o n antagonists  disrupted  a s p e c t s of male s e x u a l neuroleptics antagonist  of t y p i c a l and a t y p i c a l DA  both a n t i c i p a t o r y and consummatory  behavior  i n Experiment I I . The t y p i c a l  h a l o p e r i d o l and pimozide, and t h e DI s e l e c t i v e  SCH 23390, dose-dependently decreased the number of  l e v e l changes, i n c r e a s e d  t h e i n t r o m i s s i o n l a t e n c i e s , and  decreased the number o f mounts with i n t r o m i s s i o n and the t o t a l number of e j a c u l a t i o n s . the  D2-selective  antagonist  changes and i n c r e a s e d affect  The a t y p i c a l n e u r o l e p t i c c l o z a p i n e and s u l p i r i d e reduced the number of l e v e l  the i n t r o m i s s i o n l a t e n c i e s , but d i d not  the number of i n t r o m i s s i o n s .  Unlike  a l s o reduced t h e number of e j a c u l a t i o n s . antiemetic  but d i d not a f f e c t other  In c o n t r a s t , the  measures of s e x u a l  Higher doses of h a l o p e r i d o l , pimozide, and c l o z a p i n e  d e l a y e d or a b o l i s h e d copulatory  clozapine  agent metoclopramide reduced the number of  intromissions behavior.  sulpiride,  l e v e l changes and the i n i t i a t i o n of  behavior.  Currently,  i t i s unclear  these a s p e c t s of s e x u a l  where DA a n t a g o n i s t s  behavior  i n t h e male r a t .  p e r i p h e r a l e f f e c t i s u n l i k e l y , given DA a n t a g o n i s t  act to disrupt Although a  that the p e r i p h e r a l l y - a c t i v e  domperidone has no e f f e c t on the c o p u l a t o r y  behavior  of  intact,  sexually active  the c e n t r a l  sites  behavior  male r a t s  date,  of  the actions have n o t  o n l y two s t u d i e s  antagonists of  for  the  display  of  t h o s e two s t u d i e s , of doses of  area  the e f f e c t  of u n i l a t e r a l  MPOA was e x a m i n e d on t h e c o p u l a t o r y active  males  (Pehek e t  significantly intromitted,  t h e s e doses of  ejaculated.  and i n c r e a s e d t h e  this  effect  with  20 ug o n l y .  increased  t h e MPOA a f f e c t e d sexually active  both the  range of doses of  of  of  of  a range to  intact,  the  sexually  20 and 40 u g ,  that  mounted,  displayed  copulation, number  of  intervals.  latencies,  although  following  treatment  b o t h D I and D2 r e c e p t o r s  initiation  the D l - s e l e c t i v e  infusions  intromission  that  significance  t h o s e two s t u d i e s  copulatory behavior  dose,  rats  the e j a c u l a t i o n  of  first  the  and r a t e  of  in  copulation  in  males.  The s e c o n d o f  highest  In the  region  for  cis-flupenthixol  of  To  critical  inter intromission  blockade  sexual  DA r e c e p t o r  decreased the t o t a l  reached s t a t i s t i c a l Thus,  of  Two d o s e s ,  In rats  cis-flupenthixol  These d o s e s a l s o  unilateral  1988c).  on t h e  infusions  behavior  reduced the p r o p o r t i o n or  ejaculations  al.,  1981),  (MPOA), a t e r m i n a l  i n male r a t s .  t h e m i x e d D1/D2 a n t a g o n i s t  al.,  extensively.  DA s y s t e m , w h i c h i s  behavior  et  DA a n t a g o n i s t s  been s t u d i e d  in the medial preoptic  copulatory  (Palaschi  have examined t h e e f f e c t  incertohypothalamic of  rats  of  intact,  examined t h e e f f e c t  anatagonist  sexually active  t o t h e MPOA ( H u l l  10 u g , s i g n i f i c a n t l y latencies  et a l . ,  of  SCH 23390 on rats  the  following  1990).  The  i n c r e a s e d b o t h t h e mount  and d e c r e a s e d t h e number o f  a  mounts  and  with  intromission. obtained  These e f f e c t s  f o l l o w i n g systemic  Experiment  II.  However,  were n e a r l y  identical  administration  the D2-selective  i n c r e a s e d mount and i n t r o m i s s i o n  intromission  MPOA, s u g g e s t i n g t h a t  D I and D2 r e c e p t o r s  actions  on t h e  initiation  those  drug  in  LY 163502  and d e c r e a s e d  following  of  this  agonist  latencies  number o f m o u n t s w i t h  opposite  of  to  infusions  also  the  to  the  i n t h e MPOA may have  c o p u l a t i o n and  copulatory  rate. Little sexual  i s known a b o u t t h e r o l e  behavior  o f male r a t s .  apomorphine does n o t of  sexually active  either  the nucleus  both of  behavior  mesolimbic  et a l . ,  in the antipsychotic  release  nonselectively  (Lane & B l a h a , clozapine  10 m i n o f is  al.,  and s u l p i r i d e  affect  also  effects  evidence  of  and p i m o z i d e  atypical  DA r e l e a s e  accumbens, whereas t h e a n t i e m e t i c  affects  DA r e l e a s e  1986).  In Experiment  II,  that  selectively  in the s t r i a t u m  both t y p i c a l  1983).  affect  neuroleptics  agent  role  DA a n t a g o n i s t s  1 9 8 6 ; W h i t e & Wang,  nucleus  selectively  ex  copulatory  i n b o t h t h e n u c l e u s accumbens and In contrast,  to  1986),  DA s y s t e m s p l a y a d i f f e r e n t i a l  s u c h as h a l o p e r i d o l  1986).  behavior  infusions  et  the  agonist  the copulatory  (Hull  There  1 9 8 4 ; Lane & B l a h a ,  neuroleptics  in  i n DOPA c o n c e n t r a t i o n  and e x t r a p y r a m i d a l  Typical  DA t e r m i n a l s  unilateral  following  1987).  and m e s o s t r i a t a l  (Chiodo & Bunney,  following  an i n c r e a s e  these regions  (Ahlenius  affect  accumbens o r s t r i a t u m  vivo analyses demonstrate within  other  A l t h o u g h t h e DA r e c e p t o r  significantly  male r a t s  of  in  DA  striatum s u c h as the  metoclopramide (Lane & B l a h a ,  and a t y p i c a l  neuroleptics  117 d i s r u p t e d a n t i c i p a t o r y s e x u a l behavior and t h e i n i t i a t i o n of c o p u l a t o r y b e h a v i o r , whereas t y p i c a l n e u r o l e p t i c s and metoclopramide reduced It  the number of mounts with  i s thus p o s s i b l e t h a t mesolimbic  intromission.  DA t e r m i n a l s a r e i n v o l v e d i n  the d i s p l a y o f a n t i c i p a t o r y s e x u a l behavior and the i n i t i a t i o n o f c o p u l a t i o n whereas m e s o s t r i a t a l DA t e r m i n a l s a r e i n v o l v e d i n t h e d i s p l a y of mounts with i n t r o m i s s i o n .  However, some of these  f u n c t i o n s may be shared with d i e n c e p h a l i c DA systems,  most  n o t a b l y t h e MPOA. To f u r t h e r e v a l u a t e the r o l e of mesolimbic,  mesostriatal,  and d i e n c e p h a l i c DA t e r m i n a l s i n the s e x u a l m o t i v a t i o n and c o p u l a t o r y behavior of male r a t s , Experiment e f f e c t s of h a l o p e r i d o l  following b i l a t e r a l  I I I examined t h e  infusions to either  the nucleus accumbens or s t r i a t u m , and u n i l a t e r a l  infusions to  the MPOA.  Method S u b j e c t s and Surgery The male Long-Evans r a t s used purchased I and I I .  I I I were  from C h a r l e s R i v e r Canada and housed as i n Experiments The s t i m u l u s females used  i n Experiments females  i n Experiment  I and I I .  as i n t h e p r e v i o u s  i n Experiment  I I I were  Sexual r e c e p t i v i t y was induced  used  i n the  experiments.  T h i r t y male r a t s were g i v e n 10 t e s t s of c o p u l a t o r y behavior i n t h e b i l e v e l chambers p r i o r t o Experiment  I I I and a l l achieved  the c r i t e r i a  i n Experiment  f o r sexual experience o u t l i n e d  I (Page  118 59).  The 30 r a t s  guide cannulae  were  (Plastics  n u c l e u s accumbens All  implanted with  One, -Roanoke, VA) a i m e d a t  (n=10), dorsal  s u r g e r y was p e r f o r m e d u n d e r  (Somnitol,  60 m g / k g )  t h e s c a l p was c u t , the s k u l l .  the mediolateral  striatum  retracted,  stereotaxic  and f o u r  lowered to the a p p r o p r i a t e  for  implants  offset  cannula  o f P a x i n o s and Watson  implants  from the surface  or s t r i a t u m  Pellegrino, implantation coordinates  the brain)  Pellegrino,  reported  (AP:  cannulae,  were i n s e r t e d .  longer  Following surgery,  44x21x23 cm p l a s t i c  least  according  one week o f  - 7 . 0 mm  of cannula  t h e method  To p r o t e c t steel  and  guide  obdurators  than the  guide  t h e males  holding  to  unilateral  Unilateral  (1988).  3.0  0 . 7 mm, ML:  Rats r e c e i v e d  27-gauge s t a i n l e s s  One, R o a n o k e , V A ) , s l i g h t l y  They w e r e g i v e n a t  mm, ML:  according to the a t l a s  i n Pehek e t a l .  in  surrounded  2 . 4 mm, ML: 0 . 2 mm, DV:  (Plastics  individually  were  w i t h t h e ML  the brain)  and Cushman ( 1 9 7 9 ) .  i n use,  cannulae  bilateral  1.7  i n t h e MPOA was c h o s e n t o r e p l i c a t e  c a n n u l a e when n o t  housed  of  (1982).  t o t h e MPOA ( A P : of  (AP:  into  above  and g u i d e  the b r a i n ,  2 . 6 mm, DV: - 4 . 0 mm f r o m t h e s u r f a c e the a t l a s  the s k u l l  Rats r e c e i v e d  of  14° l a t e r a l l y )  Briefly,  cement t h a t  accumbens  mm, DV: - 6 . 5 mm f r o m t h e s u r f a c e coordinates  into  screws u s i n g d e n t a l  to the nucleus  anesthesia  The g u i d e c a n n u l a e  b o t h t h e s c r e w s and t h e c a n n u l a e . cannula  o r MPOA ( n = 1 0 ) .  frame.  each r e g i o n ,  depth.  the  screws were i n s e r t e d  h o l e s were d r i l l e d  coordinates  anchored t o the s k u l l  (n=10),  steel  either  sodium p e n t o b a r b i t a l  u s i n g a Kopf  Small burr  23-gauge s t a i n l e s s  were  chambers.  recovery before  testing.  119 Drug  Treatment Haloperidol  few drops 1, via  5,  of  (McNeil)  glacial  acetic  1 0 , and 20 p g / p l .  27-gauge  constant  injection  volume of  driven  3H1A) a t  of  acid to  Doses o f cannulae  1 jul.  an e l e c t r i c a l l y a rate  was d i s s o l v e d  All  water  obtain concentrations  haloperidol  (Plastics  central  infusion  1 pl/min.  in d i s t i l l e d  were  VA)  0,  in  w e r e made  pump (Sage I n s t r u m e n t s  The v e h i c l e  of  a  administered  One, R o a n o k e ,  injections  with  solution  a  using  Model  s e r v e d as  the  control. Apparatus The b i l e v e l  testing  were used i n E x p e r i m e n t Behavioral  Testing  chambers used i n E x p e r i m e n t s  and  II  III.  Procedures  The m a l e r a t s w e r e g i v e n s i x behavior  I  beginning at  least  postsurgical  1 week a f t e r  tests  surgery.  of  sexual  These  tests  w e r e 25 m i n i n d u r a t i o n and w e r e c o n d u c t e d one e v e r y 4 d a y s during the middle t h i r d of  these t e s t s ,  solution  after  Microinjections  for  injection  cannula,  which a s e x u a l l y  chambers  the  of  of  infusions,  for  of  the  two  vehicle  the  obdurator  for  30 s  solution  back  each m a l e was  a 5-min t e s t  of  f e m a l e was p l a c e d  each mount,  first  bilevel  in place  the d i f f u s i o n  receptive  The o c c u r r e n c e  i n one o f  w h i c h was l e f t  Following the  the b i l e v e l  20 m i n .  During the  w e r e made b y r e p l a c i n g  each i n f u s i o n t o p r e v e n t  i n one o f  cycle.  t h e males r e c e i v e d m i c r o i n j e c t i o n s  the guide cannula.  after  the dark  5 min b e f o r e b e i n g p l a c e d  chambers. with the  of  level i n the  intromission,  up  placed  changing chamber and  120 ejaculation derived I  was r e c o r d e d  t h e same m e a s u r e s o f  and I I  (Page 5 9 ) .  All  copulatory behavior  conducted.  nucleus of  each t e s t .  0,  tests  or  1 0 , and 20 ug o f  it  Experiments  sexual behavior four  did  equate the t o t a l  were  doses  design,  0,  1 , 5,  and 10  to  the  ug/side  cannula placements  to  Although  damage d u r i n g  of  5 min  cannula placements  haloperidol.  tissue  and  tests.  e q u a t e t h e amount o f d r u g d e l i v e r e d  equate the degree of  implantation,  of  which  changing  according to a l a t i n i z e d  Males w i t h u n i l a t e r a l  procedure d i d not  level  t h e males r e c e i v e d  Males w i t h b i l a t e r a l  2,  used i n  two p o s t s u r g i c a l  accumbens and s t r i a t u m r e c e i v e d  MPOA r e c e i v e d  each  first  experimental  administered  haloperidol.  tissue,  30 m a l e s d i s p l a y e d  During these t e s t s ,  haloperidol,  event r e c o r d e r ,  sexual behavior  during the  Four subsequent  before  on a c o m p u t e r i z e d  per  the this  unit  df  cannula  amount o f d r u g r e c e i v e d  by  rat.  Histology After  each e x p e r i m e n t ,  pentobarbital  (60 m g / k g )  removed and s t o r e d brains  frozen  mounted on g l a s s  microscope. t h e males  and d e c a p i t a t e d ,  Examination of  in a cryostat  slides,  the slides  target  in Figures  13 t o  structures! 15.  solution..  that  ending i n  The c a n n u l a p l a c e m e n t s  were  The  and 40-um  indicated  sodium  brains  and e x a m i n e d u n d e r  i n e a c h g r o u p had c a n n u l a t r a c k s  respective  and t h e i r  i n a 40% f o r m a l i n / s u c r o s e  were s u b s e q u e n t l y  were c u t ,  males were a n e s t h e t i z e d w i t h  sections  a the a l l  of  their are  shown  121 Figure 13.  B i l a t e r a l cannula placements (n = 10) directed at the nucleus accumbens i n Experiment I I I .  +0.2  mm  122  124 Statistical  Analyses  The e f f e c t s anticipatory  doses of  u s i n g the data of  the sexual behavior  were a s s i g n e d . differences displayed  Where a p p r o p r i a t e ,  level  of  changes, mounts,  was a s s e s s e d u s i n g c h i - s q u a r e  multiple  sexual  level  Experiment corrected method  I, for  i n each g r o u p  analysis;  of  Because a l l  elevated  p_<.05,  and  of  two-tailed.  t h e measures o f  1987).  alpha for  ANOVA, p o s t - h o c  error  The  comparisons  of  to  sexual  using the  .005.  the  11  the  behavior  statistically  As i n E x p e r i m e n t  e a c h ANOVA was  that  ejaculations  o f v a r i a n c e w i t h d o s e as  experiment-wise  & Rhodes,  the  ( s e e Page 59) were s u b j e c t e d  analyses  scores  i n each dose c o n d i t i o n  intromissions,  tests,  that  no a r b i t r a r y  the significance  rats  of  compared  t h e s e p a r a t e ANOVAs r u n on t h e s e m e a s u r e s  Bonferroni  significant  on m e a s u r e s  were  c h a n g i n g w e r e f o u n d t o be r e l a t e d  (Overall  adjusted  behavior  within-subjects  repeated measure. except  those r a t s  under  in the percentage  measures of  haloperidol  and c o n s u m m a t o r y s e x u a l b e h a v i o r  statistically displayed  of d i f f e r e n t  II, For  effects  in  were Bonferroni the each of  each  d o s e w e r e made u s i n g t h e T u k e y m e t h o d .  Results Nucleus  Accumbens  None o f rats  t h e doses of  that displayed  ejaculations. haloperidol  level  haloperidol  decreased the percentage  changing, mounts,  The ANOVA d e t e c t e d  intromissions,  a significant  on L C , F( 3 , 27 ) =10 . 0 9 , p_< . 00026  overall  (Figure  16),  or  effect but  of  not  of  125  F i g u r e 16.  E f f e c t of b i l a t e r a l i n f u s i o n s of d i f f e r e n t doses of h a l o p e r i d o l t o the nucleus accumbens on the 9 primary measures of male s e x u a l behavior observed i n Experiment I I I . Values a r e means + SE. * * p_<.05, * p_<.01, from c o n t r o l v a l u e s .  MEAN LATENCY  MEAN NUMBER  0  • i i i i i i i i i i i—i—i—•—i  a  1 •  • i  » i  i  s  MEAN NUMBER  (soc)  s  i  i—i—i—J—i—i  i  i  H  .  .  .  .  s  ;  s  s  8  • •  z  MEAN NUMBER  MEAN LATENCY  J—i—i—i—i—i—i—i—i i • • • i i i  MEAN NUMBER J  1 1  »  1  u  I I  »  I I  -i  i  i  i  •  MEAN LATENCY § 8 8 i  i — J — i  i  MEAN LATENCY  (soc)  I 3 . f i •  i  (soc) 8  i • i  i  8 f t • • • i  i  8 i  i  8  i  (soc) i  MEAN LATENCY i  8  ft  8  8  J—i—i—i—i—i—i—'  8  i  i  8  i  (soc) •  8  •  i  8  i  127 on a n y o t h e r revealed  measure o f  that  sexual  the highest  dose,  LC compared t o t h e e f f e c t of  the  lower  behavior.  of  Post-hoc  10 j u g / s i d e ,  the c o n t r o l  comparisons  significantly  solution  reduced  or t h e  effect  doses.  Striatum None o f rats  that  t h e doses of  displayed  ejaculations. haloperidol  level  changing,  The ANOVA d e t e c t e d  measure o f  that  sexual  the highest  or t h e e f f e c t  of  Medial Preoptic None o f rats  the  ejaculate.  t h e doses of  (Figure  that  the e f f e c t  Post-hoc  of  or  effect  17),  but  of  not  comparisons  significantly the c o n t r o l  solution  doses.  changing,  of  haloperidol  systemic  The ANOVA d e t e c t e d  decreased the percentage  mounts,  received the highest  t o those of  18).  (Figure  10 j u g / s i d e ,  haloperidol  level  The e f f e c t s  very similar  p_<.005  overall  of  Area  that displayed  O n l y one r a t  lower  intromissions,  a significant  behavior.  dose,  i n c r e a s e d t h e NE c o m p a r e d t o  decreased the percentage  mounts,  on t h e NE, F( 3 , 2 7 ) = 5 . 4 5 ,  on a n y o t h e r revealed  haloperidol  dose  or  intromissions.  (20 jug)  infusions  administration significant  of  failed  to  t o t h e MPOA were i n Experiment  overall  effects  II  of  haloperidol  on L C , F( 3 , 27 ) =53 . 5 3 , p_<.0001; t h e L C L , F ( 3 , 27 ) =5 . 5 7 ,  p_<.005;  IL,  p_<.0009; p_<.0003.  the  F( 3 , 27 )=12 . 4 8 , p_<.0001; t h e N I , F( 3 , 27 )=7 . 8 6 ,  t h e NE, F ( 3 , 27 ) = 5 . 6 2 , p_<.005;  A l t h o u g h t h e ANOVA d e t e c t e d an e f f e c t  t h e ML, F( 3 , 2 7 ) = 4 . 5 9 , of  and t h e  statistical  p_<.02,  significance  this  effect  I R , F( 3 , 27 ) =9 . 7 5 , of  haloperidol  d i d not reach the  r e q u i r e d by t h e  Bonferroni  on  level  128  Figure  17.  E f f e c t of b i l a t e r a l i n f u s i o n s of d i f f e r e n t doses of h a l o p e r i d o l t o t h e s t r i a t u m on t h e 9 p r i m a r y m e a s u r e s o f male s e x u a l b e h a v i o r o b s e r v e d i n E x p e r i m e n t I I I . V a l u e s a r e means + SE. * p_<.05,  * pK.Ol,  from c o n t r o l  values.  MEAN NUMBER  MEAN LATENCY 8  j  i  i  i  i  i  i  i  6  8  8  MEAN NUMBER  (soc) 8  8  i—i—i  •  •  •  •  '  •  •  '  1  1  1  '  '  1  '  1  •  1  • •  T  2  MEAN LATENCY (soc) i 8 8 8  MEAN LATENCY 8 J — i  8 i  i  8  (soc)  8  i — i — i — i  8 i  i  8 i  i  m  MEAN NUMBER  MEAN LATENCY (soc) 8 8 8 8  MEAN LATENCY 8  8  8  J — i — i — i — i — i — i — i  8  (soc) i  8 i  i  8 i  130  F i g u r e 18.  E f f e c t of u n i l a t e r a l i n f u s i o n s of d i f f e r e n t doses of h a l o p e r i d o l t o the medial p r e o p t i c area on the 9 primary measures of male s e x u a l behavior observed i n Experiment I I I . Values a r e means + SE. * * p_<.05, * p_<,01, from c o n t r o l v a l u e s .  MEAN NUMBER J  i i i i i—i  i—i  MEAN LATENCY  i i i i • • i  (soc) 8  6*  i • i i i i i i i i i i  i—i  8  &  8  8  8  MEAN NUMBER O t # « * » O M * o > £ 8 • ' • ' '  1  1  '  1  ' '  ' ' ' • ' • * •  1  z 2  MEAN NUMBER J  i i i i i i i  MEAN LATENCY ii  -i  § i  i  8 i—i  (soc) 8 i  '  MEAN LATENCY 8 •  8  6  8  J—i—i—i—i—i  (soc)  8  i  •  •  8  8  •  • •  m  MEAN LATENCY j  § i  i  8 i  i  (soc) 8 •  i  8 i  MEAN LATENCY 8  6  8  J—i—i—i—i—i—i  8  i  (soc) i  8  8  • • •  132 correction. revealed the  Post-hoc  that  the  comparisons  the e f f e c t  of  each dose  10 and 20 jug d o s e s s i g n i f i c a n t l y  I L compared t o t h e e f f e c t s  lower doses,  of  whereas o n l y t h e  of  the c o n t r o l  r e d u c e d LC and  solution  20 ^pg d o s e s i g n i f i c a n t l y  t h e LCL and d e c r e a s e d t h e N I , NE, and IR compared t o of  the control  solution  Interestingly,  and t h e  only three  lower of  female  copulatory  w h e r e a s none o f  activity  ug d o s e p u r s u e d t h e bottom l e v e l toward the This  throughout  result  These r a t s  the  level  the r a t s  however,  increase  were c a p a b l e  n o r m a l amount o f  of  the  t h e EL o r  completing the  time.  Thus,  behavior  the  effects  that  received  to the  that  infusions  in the b i l e v e l  the  or  did  series to  not these in  a  t h e MPOA  measure  chambers:  20  bottom.  most o f  copulatory  uncharacterized  the  oriented  haloperidol  indicates  10 of  s t a y e d on  a g e n e r a l motor  that  first  the  d u r i n g bouts  although a l l  of  haloperidol  may h a v e d i m i n i s h e d a r e l a t i v e l y consummatory s e x u a l  fact III  increased  received  typically  20-min t e s t ,  c o u l d be t a k e n as e v i d e n c e  significantly  the  to  that  f e m a l e as she moved f r o m t h e t o p l e v e l  sensory d i s r u p t i o n ;  rats  from l e v e l  female.  the  doses.  the r a t s  ug d o s e p u r s u e d t h e  and  of  pursuit  of  female.  Discussion Experiment affects behavior regions.  III  provides  anticipatory  first  evidence t h a t  and c o n s u m m a t o r y a s p e c t s  o f male r a t s Bilateral  the  selectively  infusions  of  of  in d i f f e r e n t haloperidol  the  haloperidol sexual  DA t e r m i n a l  to the  nucleus  accumbens, a major t e r m i n a l  of the mesolimbic A10 pathway,  a t t e n u a t e d l e v e l changing without a f f e c t i n g other measures of sexual  behavior s i g n i f i c a n t l y .  h a l o p e r i d o l to the striatum, A9 pathway, i n c r e a s e d during  i n f u s i o n s of  a major t e r m i n a l  of t h e m e s o s t r i a t a l  t h e t o t a l number of e j a c u l a t i o n s  t h e 20-min t e s t .  haloperidol  Bilateral  Finally, unilateral  t o the MPOA, a major t e r m i n a l  displayed  i n f u s i o n s of  of the i n c e r t o -  hypothalamic A14 pathway, produced n e a r l y a l l of t h e e f f e c t s of systemic administration, changes, i n c r e a s e d of  intromissions  terminals  i n c l u d i n g a decreased number of l e v e l  intromission  l a t e n c i e s , and a decreased number  and e j a c u l a t i o n s .  These r e s u l t s suggest t h a t DA  i n t h e nucleus accumbens and s t r i a t u m a r e i n v o l v e d i n  the d i s p l a y of  a n t i c i p a t o r y sexual  behavior and c o p u l a t o r y  rate,  r e s p e c t i v e l y , whereas DA t e r m i n a l s  i n the MPOA are i n v o l v e d i n  the d i s p l a y of a n t i c i p a t o r y s e x u a l  b e h a v i o r , the i n i t i a t i o n of  copulation,  copulatory  r a t e , and h i t r a t e .  The e f f e c t s of h a l o p e r i d o l consistent  with p r e v i o u s r e p o r t s  mixed D1/D2 a n t a g o n i s t antagonist of s e x u a l 1988c).  i n f u s i o n s t o t h e MPOA a r e that u n i l a t e r a l  i n f u s i o n s of t h e  c i s - f l u p e n t h i x o l or the D l - s e l e c t i v e  SCH 23390 t o the MPOA d i s r u p t the i n i t i a t i o n and r a t e behavior i n male r a t s  Although DA t e r m i n a l s  important m u l t i f a c e t e d  ( H u l l e t a l . , 1990; Pehek e t a l . , i n t h e MPOA appear t o p l a y an  r o l e i n t h e c o n t r o l of a n t i c i p a t o r y and  consummatory a s p e c t s of male sexual e f f e c t s observed f o l l o w i n g  b e h a v i o r , s e v e r a l of the  i n f u s i o n s of h a l o p e r i d o l t o t h e MPOA  may be due t o a common mechanism.  Pehek et a l . (1988a) have  134 shown t h a t  systemic  latency to  first  intact,  of  that  penile  reflexes.  intromission  intromissions  reflects  which d i s r u p t s  c a n be a t t r i b u t e d  changes c a n n o t . important behavior  rats  for  lesions  a sexually  affect  control  of  consistent  be a r g u e d t h a t  the d i s p l a y  for  of  systemic  penile  with a recent  for  the of  administration  rate,  female  anticipatory  in  hit level  sexual  is consistent  with  (Edwards & E i n h o r n ,  infusions  to the  d e c r e a s e d t h e number o f did not  significantly  behavior,  sexual behavior. that  This  bilateral  a secondary sexual r e i n f o r c e r  of  male  1986).  nucleus  level  changes. affect  suggesting  accumbens p l a y a s e l e c t i v e  report  DA  and  t h e MPOA d e c r e a s e t h e p r e f e r e n c e  infusions  anticipatory  of  role  suggestion infusions  a m p h e t a m i n e t o t h e n u c l e u s accumbens c a n r e s t o r e responding  activation  t h e MPOA c o n t r i b u t e s  suggestion  receptive  in the nucleus  the  reflexes.  initiation,  the d i s p l a y  This of  that  c o n s u m m a t o r y m e a s u r e s o f male s e x u a l terminals  the sympathetic  in  have  t o such a mechanism, t h e decrease  accumbens s i g n i f i c a n t l y haloperidol  (1988b)  the antagonism of d i e n c e p h a l i c  As w i t h t h e MPOA, h a l o p e r i d o l  However,  al.  the  erections  apomorphine t o e i t h e r  of c o p u l a t o r y  i n male r a t s .  evidence t h a t  of  following  This suggests  information  increase  l a t e n c y and d e c r e a s e d number  Although the d i s r u p t i o n rate  Pehek e t  may t h e r e f o r e  and e j a c u l a t i o n s  DA a n t a g o n i s t s  terminals,  nucleus  It  haloperidol  and d e c r e a s e t h e number o f  infusions  paraventricular  increased  of  erection  of  s e x u a l l y a c t i v e male r a t s .  also demonstrated MPOA o r  administrations  rates  following  of  that in  DA  the  is of operant  lesions  of  135 the b a s o l a t e r a l  amygdala  i n male r a t s  consummatory measures of It  is  also consistent  DA t e r m i n a l s preparatory (e.g.,  Kelley  electrolytic  & Stinus, lesions  have been r e p o r t e d  following  t h e A10 c e l l  of  to the nucleus  haloperidol,  or  of  other  of  male s e x u a l b e h a v i o r  behavior However, that  1986).  in Moreover,  in the nucleus  of  in this  were  active  observed  accumbens.  haloperidol  experiment  infusions  accumbens  in sexually  the nucleus  DA a n t a g o n i s t s ,  accumbens  and P E I s  these e f f e c t s  to  needs t o be e x a m i n e d on a n t i c i p a t o r y  of  i n t h e VTA  et a l . ,  selectivity  The e f f e c t  1978).  latencies  None o f  accumbens  feeding  latencies  DA t e r m i n a l s  behavioral  viewed c a u t i o u s l y .  of  1989).  implicating  DA i n t h e n u c l e u s  of  haloperidol  al.,  evidence  bodies  (Brackett  1989).  et  in the control  rats  i n c r e a s e mount  et a l . ,  infusions  of  i n c r e a s e mount  to  the apparent  infusions  accumbens  77% d e p l e t i o n to  have been r e p o r t e d  Thus,  of  6-OHDA l e s i o n s  (Robbins  body of  1 9 8 5 ; Koob e t a l . ,  sexually active  bilateral  rats  with a large  affecting  (Everitt  not consummatory a s p e c t s  p r o d u c e d an a v e r a g e  intact,  sexual behavior  i n the nucleus but  without  of  higher  should doses  to the nucleus  be of  accumbens  or consummatory a s p e c t s  before the r e s u l t s  reported  of  h e r e c a n be  generalized. Infusion  of  the highest  increased the t o t a l 20-min t e s t , serve  number o f  suggesting that  t o d e l a y or  inhibit  dose o f  haloperidol  ejaculations  unexpected because t h e s y s t e m i c  striatum  displayed during  DA t r a n s m i s s i o n  ejaculation.  to the  the  i n t h e s t r i a t u m may  This r e s u l t  administration  of  was haloperidol  136 decreased,  rather  than  increased,  ejaculations  i n Experiment  to  but  the  large  latency  II.  nonsignificant  the t o t a l  However,  this  decrease  in the  observed w i t h the h i g h e s t  electrolytic  lesions  of  dose.  t h e A9 c e l l  n i g r a pars compacta t h a t  latencies,  d e c r e a s e t h e number o f (Brackett  et  al.,  bodies  to  1986).  of  et  al.,  were o b s e r v e d  striatum. role  Clearly,  more work  of m e s o s t r i a t a l  rats.  following  ejaculations  following  infusion  to the s t r i a t u m  this  c a n be s t a t e d  It  is d i f f i c u l t  unilateral of  tissue  not  infusions  structure  midline;  surrounds  however,  those to  the  behavior  t h e same o r  higher  the  exact of  male of  doses  of  the r e l i a b i l i t y  of  bilateral  b e c a u s e t h e amount o f d r u g  Unilateral,  latencies  i n c r e a s e d number  t o compare t h e r e s u l t s  of  dorsal  of  certainty.  tissue  rather  MPOA w e r e e m p l o y e d i n E x p e r i m e n t this  to specify  the  the  haloperidol  required before  with  and t h e m a g n i t u d e  equated.  is  of  of  of  and  rats  None o f  in the sexual  a replication  haloperidol effect  is required  DA t e r m i n a l s  In p a r t i c u l a r ,  of  DA  and  t h e mount  1989).  infusions  of  intromissions,  6-OHDA l e s i o n s increase  effects  56% d e p l e t i o n  in sexually active  Bilateral  (Robbins  substantia  i n c r e a s e mount  to  rats  may be due  ejaculation  in the  s t r i a t u m have a l s o been r e p o r t e d sexually active  effect  d e c r e a s e t h e number o f ejaculations  of  Interestingly,  p r o d u c e d an a v e r a g e  i n t h e s t r i a t u m have been r e p o r t e d intromission  number  III  the t h i r d  using the atlas  per  unit  trauma d u r i n g s u r g e r y  were  than b i l a t e r a l , for  infused  and  infusions  two r e a s o n s .  ventricle  very close  of P e l l e g r i n o  et  al.  to  the  First, to  the  (1979)  the  137 dorsal but  portion  rather  of  t h e MPOA i s  not  bisected  f o r m s a n a r r o w and c o n t i n u o u s  nucleus.  The d i f f e r e n c e  infusions  to this  accumulating narrowness  area i n terms of  and  ventricle  midline  unilateral  t h e amount o f  drug  s h o u l d have been m i n i m a l g i v e n  the s t r u c t u r e .  w o u l d have r e q u i r e d  bilateral  between b i l a t e r a l  in the t i s s u e  of  by t h e t h i r d  In addition,  bilateral  t h e c a n n u l a e t o be p l a c e d  into  implantation  the  brain  e x t r e m e l y a c u t e a n g l e s b e c a u s e t h e c a n n u l a e w e r e much t o o t o be p l a c e d p a r a l l e l the  liklihood  unilateral  t o one a n o t h e r .  of misplacement.  cannula  m e t h o d u s e d b y Pehek e t a l .  to  bilateral trauma  so t h a t  of  l n Experiment  haloperidol  However,  the  infusion  in size.  haloperidol relatively  Instead,  choosing  in  that  although  equivalent  to  comparing the e f f e c t s  of  Although the r e s u l t s acts  in Experiment  i n each o f III  these  suggest  III  20 ug o f  bilaterally  c a u t i o n must be t a k e n  Experiment  of  surface  t o t h e MPOA was v i e w e d  haloperidol of  doses  b y each r a t ;  10 u g / s i d e d e l i v e r e d  Nevertheless,  similar  tissue  and MPOA v a r y  t h e method e m p l o y e d  unilaterally  the  comparison  of drug t o  striatum,  amount o f d r u g r e c e i v e d  delivered  accumbens.  haloperidol  of  w o u l d n o t have e q u a t e d t h e r a t i o  equated the o v e r a l l  nucleus  a direct  cis-flupenthixol III.  a r e a because t h e n u c l e u s accumbens, greatly  large  increased  i m p l a n t a t i o n ' w o u l d h a v e e q u a t e d t h e amount o f  incurred during surgery,  at  t h e MPOA was t o r e p l i c a t e  (1988),  c o u l d be made b e t w e e n t h e e f f e c t s s t u d y and h a l o p e r i d o l  T h i s c o u l d have  The s e c o n d r e a s o n f o r  implantations  the  as to  the  when  structures.  that  i n t h e n u c l e u s accumbens and MPOA t o  decrease  138 anticipatory  sexual behavior,  diencephalic  structures  of  copulation,  out.  to disrupt  an a c t i o n on o t h e r  In particular,  mesolimbic  accumbens may p l a y a r o l e noted above,  bilateral  amygdala reduce r a t e s male r a t s  for  presentation  and i n t h e MPOA o r  terminals  of  responding  copulation  Although the nearby c o r t i c o m e d i a l of  demonstrated 1987).  DA f i b e r s  The o l f a c t o r y  projection  tubercle  f r o m t h e VTA.  t u b e r c l e do n o t a f f e c t male r a t s of  this  (Perkins  structure  An e x h a u s t i v e needed. nucleus  (reviewed  lesions  et a l . , affect  1980),  it  anticipatory  is  sexual  study of d i e n c e p h a l i c  done t o e x a m i n e t h e r o l e  of  the of  other  t h e median eminence r e c e i v e s  A13 c e l l  bodies  have in  1987),  and t h i s  been  Herkenham,  olfactory in lesions  behavior.  of  penile  copulation,  also  reflexes  little  has  been  DA t e r m i n a l s .  a DA p r o j e c t i o n  structure  is  suprachiasmatic  i n t h e m e d i o b a s a l and a r c u a t e n u c l e i  (Moore,  large  known w h e t h e r  diencephalic  example,  a  copulation  i n t h e MPOA and  consummatory measures o f  1989).  DA t e r m i n a l s  in the c o n t r o l  active  a m a j o r DA  of  not  As  affecting  et a l . ,  also receives  nucleus  the  amygdala r e c e i v e s  consummatory measures  have been i m p l i c a t e d  hypothalamus  in sexually  (Everitt  ruled  basolateral  female w i t h o u t  amygdala  Although  A l t h o u g h DA t e r m i n a l s  and c e r t a i n  the  f r o m t h e VTA, DA r e c e p t o r s  in the basolateral  be  behavior.  associated with  a sexually receptive of  of  aspects  than the  sexual  lesions  a secondary stimulus  cannot  other  in anticipatory  operant  consummatory  DA t e r m i n a l s  excitotoxic of  consummatory measures  projection  certain  other  has  from of  been  the  the  For  139 implicated  in the d i s r u p t i o n  hyperprolactinemia hypothesized  (Bartke  to act  of  et  male s e x u a l  al.,  as a " p r o l a c t i n  median eminence, which p a r t i a l l y agonists  s u c h as b r o m o c r i p t i n e  prolactin  1983).  and t o r e s t o r e  behavior In fact,  inhibiting  explains  by DA i s  factor"  the a b i l i t y  t o reduce c i r c u l a t i n g  sexual behavior  in  to  the  o f DA levels  of  hyperprolactinemic  males. The r e s u l t s of  DA r e c e p t o r s  of Experiment  to account  administration  of  selectivity  systemic  reducing affect  level  indicate  for  most o f  its  the  haloperidol.  the e f f e c t s  The a p p a r e n t  administrations  c h a n g i n g a t doses t h a t  of  action at m u l t i p l e  accumbens and MPOA, w h e r e a s  its  sites, ability  highest  i n t h e MPOA.  affinity  and 5-HT2 r e c e p t o r s  of  the  antagonists  of  in the nucleus  c o n s u m m a t o r y measures o f resolve  the  issue of  systemic  it  in  significantly  i n Experiment  in this  case t h e  to disrupt  D I , D2, oil,  II  may  nucleus  consummatory  a n t a g o n i s m o f DA binds  has a l o w a f f i n i t y  (Tamminga & G e r l a c h ,  high a f f i n i t y  of  although haloperidol  t o D2 r e c e p t o r s ,  2,  effects  However,  haloperidol  haloperidol  m e a s u r e s o f c o p u l a t i o n may be due t o a s e l e c t i v e receptors  antagonism  behavioral  d i d not  consummatory measures o f c o p u l a t i o n  be due t o  that  i n t h e n u c l e u s accumbens and MPOA by  are s u f f i c i e n t  of  III  1987).  for  with DI,  A comparison  and 5-HT2  recpetor  accumbens and MPOA on a n t i c i p a t o r y  sexual behavior  pharmacological  i n male r a t s  selectivity.  would  and  help  140 EXPERIMENT IV: ELECTROCHEMICAL DETECTION OF CENTRAL DOPAMINE EFFLUX DURING SEXUAL BEHAVIOR  The  IN THE MALE RAT  r e s u l t s of Experiments II and I I I c o n f i r m  that c e n t r a l  DA systems p l a y an important r o l e i n a n t i c i p a t o r y s e x u a l and  i n t h e i n i t i a t i o n and r a t e of c o p u l a t o r y  rats.  behavior i n male  Experiment I I demonstrated t h a t the s y s t e m i c  administration  of low-to-moderate doses of s e v e r a l c e n t r a l l y -  a c t i v e DA r e c e p t o r  antagonists  reduce t h e number o f l e v e l  changes, i n c r e a s e t h e mount and i n t r o m i s s i o n l a t e n c i e s , the p o s t e j a c u l a t o r y intromissions the  behavior  increase  i n t e r v a l , and/or decrease t h e number of  and e j a c u l a t i o n s .  t y p i c a l DA r e c e p t o r  Experiment I I I demonstrated  antagonist  haloperidol  that  selectively  d e c r e a s e s t h e number of l e v e l changes when i n f u s e d t o the nucleus accumbens, s e l e c t i v e l y  increases  infused to the striatum,  and a f f e c t s both a n t i c i p a t o r y and  consummatory measures o f s e x u a l systemic administration  the number of e j a c u l a t i o n s when  behavior i n a manner s i m i l a r to  when i n f u s e d t o t h e MPOA.  These d a t a  suggest t h a t a s p e c t s of the a n t i c i p a t o r y and consummatory s e x u a l behavior of male r a t s a r e r e g u l a t e d m e s o t e l e n c e p h a l i c and d i e n c e p h a l i c combined antagonism of DA r e c e p t o r s regions  d i f f e r e n t i a l l y by DA t e r m i n a l s ,  and t h a t t h e  i n a t l e a s t two of these  (the nucleus accumbens and MPOA) i s s u f f i c i e n t  the d i s r u p t i o n of a n t i c i p a t o r y and consummatory s e x u a l observed f o l l o w i n g s y s t e m i c a d m i n i s t r a t i o n  t o produce behavior  of h a l o p e r i d o l .  141 Having e s t a b l i s h e d t h a t DA r e c e p t o r s d i f f e r e n t i a l l y regulate the sexual next q u e s t i o n  i n these  behavior  terminals  of male r a t s , the  concerned the dynamics of such r e g u l a t i o n : What  k i n d of a c t i v i t y do these DA systems e x h i b i t d u r i n g behavior?  Although the r e s u l t s of Experiments II and I I I p r o v i d e  a b a s i s f o r onSy t h e most g e n e r a l has  r e c e n t l y been p r o v i d e d  electrochemical periods  sexual  i n f e r e n c e s , an i n d i r e c t  by three s t u d i e s u s i n g ex v i v o  assessments of DA and i t s m e t a b o l i t e s  of s e x u a l  answer  following  activity.  To r e i t e r a t e b r i e f l y from the I n t r o d u c t i o n , A h l e n i u s  et a l .  (1987) examined the accumulation of DOPA i n the nucleus accumbens, s t r i a t u m , septum, and a n t e r i o r hypothalamus f o l l o w i n g either  10 min of s e x u a l  activity  ( a t l e a s t one e j a c u l a t i o n )  a r e c e p t i v e female, 25 min of t r e a d m i l l locomotion, the home cage. significantly  Sexual a c t i v i t y  increased  or 10 min i n  DOPA accumulation  i n t h e s t r i a t u m and nucleus accumbens, but not i n  the septum or a n t e r i o r hypothalamus, i n comparison with rats l e f t  with  i n t h e home cage.  accumulation s i g n i f i c a n t l y three regions, suggesting  Treadmill  control  locomotion i n c r e a s e d  DOPA  i n the s t r i a t u m , but not i n the other t h a t catecholamine s y n t h e s i s  i n the nucleus accumbens as a s p e c i f i c  increases  f u n c t i o n of s e x u a l  a c t i v i t y and i n the s t r i a t u m as a n o n s p e c i f i c f u n c t i o n of e i t h e r sexual  a c t i v i t y or t r e a d m i l l  locomotion.  L e v e l s of DA and DOPAC i n the p a r i e t a l c o r t e x , r e g i o n , mediobasal hypothalamus, and lumbrosacral examined i n r a t s t h a t achieved  preoptic  cord have been  e i t h e r one e j a c u l a t i o n or  142 intromissions rats  that  et a l . ,  without  d i d not  1987).  were e l e v a t e d  ejaculation,  initiate  copulation with receptive  B o t h DA and DOPAC l e v e l s significantly  after  a l o n e was e l e v a t e d s i g n i f i c a n t l y in the  lumbrosacral  intromission,  but not  in this  descending  inhibition  intromission.  after  of  Changes  suggested t h a t  following  DA r e l e a s e  ejaculation.  utilization  but  Finally,  not release  Hoffman e t  i n t h e MPOA, a r c u a t e  (1987)  nucleus/median  alone  active  to  DA the  occur  cortex. is  increased  i n c r e a s e d DA area.  e x a m i n e d DA and DOPAC eminence,  rats  or m e d i a l  to sexual  e x h a u s t i o n or were r u n i n a m o t o r - d r i v e n w h e e l .  sexual  exhaustion condition  when mounts were ejaculation. or m e d i a l sexually  initiated  DA l e v e l s  forebrain  brain regions,  was y o k e d t o a r a t  such t h a t  copulated  in  t h e wheel s t a r t e d  and s t o p p e d r o t a t i n g  after  bundle,  were d e t e c t e d  suggesting that  However,  nucleus in  both  no d i f f e r e n c e s  among g r o u p s  DA u t i l i z a t i o n  the  each  were e l e v a t e d s i g n i f i c a n t l y rats.  Each  rotating  i n t h e MPOA, b u t n o t t h e a r c u a t e  e x h a u s t e d and a c t i v e  DOPAC c o n c e n t r a t i o n s  had e i t h e r  levels  forebrain  intact,  in the wheel-running c o n d i t i o n  that  in  These  bundle of  rat  sexually  d i d not  and u t i l i z a t i o n  in the preoptic  al.  after  during  or p a r i e t a l  Intromission  DA l e v e l s  suggesting that  i n DA o r DOPAC l e v e l s hypothalamus  region  significantly  reflexes  (Mas  w h e r e a s DOPAC  t h e c o r d may c o n t r i b u t e  ejaculatory  females  intromission.  ejaculation,  r e g i o n of  the mediobasal  results  ejaculation, after  inactive  i n the p r e o p t i c  c o r d were a l s o e l e v a t e d  mechanisms  either  compared t o s e x u a l l y  in the  may have  three been  in  attenuated  i n the MPOA f o l l o w i n g l e n g t h l y bouts of locomotor  a c t i v i t y , the manipulation and  forced a c t i v i t y  common t o both the s e x u a l  exhaustion  groups.  Taken t o g e t h e r ,  t h e r e s u l t s of these t h r e e s t u d i e s  that DA s y n t h e s i s , r e l e a s e , and/or u t l i l i z a t i o n nucleus accumbens, s t r i a t u m , and MPOA d u r i n g  suggest  increase  i n the  copulation.  However, i n the two s t u d i e s t h a t c o n t r o l l e d f o r locomotor activity  (Ahlenius  i n c r e a s e s observed copulatory  e t a l . , 1987; Hoffman e t a l . , 1987), the i n the s t r i a t u m and MPOA were not s p e c i f i c t o  behavior.  Unfortunately,  ex v i v o a n a l y s e s  permit DA a c t i v i t y t o be observed d i r e c t l y d u r i n g behavior,  thus the p a r t i c u l a r a s p e c t s  correspond t o those i n c r e a s e s  of s e x u a l  do not  sexual  behavior  that  i n DA a c t i v i t y cannot be  determined. A more d i r e c t way t o assess behavior  DA a c t i v i t y d u r i n g  i s use e l e c t r o c h e m i c a l d e t e c t i o n i n v i v o .  accomplished two ways, u s i n g voltammetry microdialysis  (Imperato & Di C h i a r a ,  Marsden, & Ungerstedt, 1983).  sexual T h i s can be  (Lane & Blaha,  1984; Z e t t e r s t r o m ,  a voltage  (e.g.,  Sharp,  Voltammetry i n v o l v e s the o x i d a t i o n  of e l e c t r o a c t i v e substances w i t h i n b r a i n e x t r a c e l l u l a r passing  1986) or  f l u i d by  -100 t o +250 mV) s e l e c t i v e f o r those  substances through a g r a p h i t e r e a c t i o n produces c u r r e n t t h a t  electrode.  The r e s u l t i n g  oxidation  i s d i r e c t l y p r o p o r t i o n a l t o the  amount of e l e c t r o a c t i v e substance o x i d i z e d a t t h e t i p of the electrode.  T h i s c u r r e n t can be d e t e c t e d  by the g r a p h i t e  electrode.  M i c r o d i a l y s i s i n v o l v e s t h e e x t r a c t i o n of  extracellular oxidation  fluid  with a microdialysis  and e l e c t r o c h e m i c a l  substances  techniques  strength  Electroactive  of  voltammetry  is  its  signal.  oxidized at  Unfortunately,  t h e same p o t e n t i a l s .  acid,  approximately  +250 mV.  be e l i m i n a t e d anionic Adams,  1984)  resolution.  at  Intervals,  1-sec  w i t h changes  by c o a t i n g  s u c h as N a t i o n  is  example,  are a l l  oxidized  the c o n t r i b u t i o n  the g r a p h i t e (Gerhardt,  paste at  Although  it  is  the t i p  of  not possible  norepinephrine  to the catecholamine  acid with  oxidation  current  inhibit  oxidation  DA i n t o  1983).  of  c a n be  inhibitor  norepinephrine.  norepinephrine signal  the  pharmacological  -hydroxylase  s u c h as t h e s e u s i n g s t e a r a t e - m o d i f i e d  the catecholamine  can  an  the c o n t r i b u t i o n  FLA-63 t o  to  anions  with  e.g.,  that  the  electrode  treatment,  have i n d i c a t e d  of  signal  in a given tissue with the appropriate  electrodes  at  oxidation  determined  Studies  c a n be  distinguish  f r o m DA, as b o t h a r e c a t i o n s ,  the c o n v e r s i o n of  recurring  (Blaha & Lane,  norepinephrine  by u s i n g t h e d o p a m i n e  the  Oke, N a g y , Moghaddam, &  the electrode chemically to  in  DA, DOPAC,  o r m i x i n g an a n i o n s u c h as s t e a r i c  graphite  a  substances  acid to the catecholamine  either  polymer  However,  An  temporal  selectivity  For  and n o r e p i n e p h r i n e  DOPAC and a s c o r b i c  and w e a k n e s s e s .  e v e n t s t o be c o r r e l a t e d  p r o b l e m w i t h v o l t a m m e t r y because s e v e r a l  ascorbic  electroactive  have s t r e n g t h s  s u b s t a n c e s may be o x i d i z e d  allowing behavioral oxidation  of  subsequent  w i t h HPLC.  Both i n v i v o important  detection  p r o b e and  graphite  paste  does n o t  contribute  i n t h e n u c l e u s accumbens  or  striatum  (Blaha & Lane,  The o p p o s i t e is  selectivity  resolution.  is  true  whereas  peaks  rates  off  for  its  Selectivity  because e l e c t r o a c t i v e elution  1983).  major  is  dialysate  20 m i n i s temporal  behavior,  period.  characteristic  However,  the e x t r a c e l l u l a r  a slow r a t e 10 o r  (e.g.,  in the detector.  examine d r u g e f f e c t s  is  analyses.  typical  ejaculate,  Any i n c r e a s e  example,  for  DA a c t i v i t y .  to perform f i n e l y  with respect  to  and  in extracellular  rat  DA l e v e l s  t h e phases o f  the  grained  to  initiate a  10-min  could  have  copulation.  As  w i t h HPLC a l l o w s  only the  observations  t o be c o r r e l a t e d  w i t h changes  this  technique  c a n be used i n a  of voltammetric  of  10 o r  microdialysis  However,  the  sexual  and resume c o p u l a t i o n w i t h i n  way t o c o n f i r m t h e s e l e c t i v i t y extracellular  once e v e r y  on DA r e l e a s e ,  a sexually active  o c c u r r e d d u r i n g one o r many o f  general behavioral  metabolites  not s u f f i c i e n t For  5 ul/min)  must  A l t h o u g h assessments  to  resolution  fluid  20 m i n t o a l l o w enough o f  sufficient  ex v i v o a n a l y s e s ,  microdialysis  to  DA and i t s  copulation,  temporal  t h e HPLC c o l u m n , g i v i n g r i s e  HPLC once e v e r y  is  strength  different  of  it  poor  assured w i t h  levels  behavioral  major  by  t o be p r e s e n t  extracellular  is  Its  are separated  from the b r a i n at  analyzed w i t h  weakness  relatively  substances  i n the chromatogram.  be e x t r a c t e d  microdialysis.  changes  with  most in  general in  DA c o n c e n t r a t i o n s .  I n Experiment  IVa,  i n v i v o v o l t a m m e t r y was u s e d t o  efflux  i n the nucleus  accumbens and s t r i a t u m ,  efflux  i n t h e MPOA, b e f o r e ,  during,  and a f t e r  and  a s s e s s DA  catecholamine  30-min p e r i o d s  of  146 copulatory IVb,  activity  i n s e x u a l l y a c t i v e male r a t s .  voltammetry was  these r e g i o n s other  while  used to assess  DA  In Experiment  or catecholamine e f f l u x  s e x u a l l y a c t i v e male r a t s were exposed  males, n o n r e c e p t i v e  females, a s l i d e c o n t a i n i n g  in  to  estrous  v a g i n a l s e c r e t i o n s , or r e c e p t i v e females behind a wire-mesh partition.  In Experiment IVc,  c o n f i r m the r e s u l t s observed accumbens and  i n v i v o m i c r o d i a l y s i s was  i n Experiment IVa  i n the  used to  nucleus  striatum.  EXPERIMENT IVa The  r e s u l t s of ex v i v o s t u d i e s suggest t h a t DA  r e l e a s e , and/or u t i l i z a t i o n and  d i e n c e p h a l i c DA  increases within  terminals  s e x u a l l y a c t i v e male r a t s . b e h a v i o r a l d e t a i l , the  first  increase  i n more  i n t e r p u l s e i n t e r v a l to assess  e f f l u x i n the nucleus accumbens and i n the MPOA, b e f o r e  of c o p u l a t i o n i n  experiment of t h i s s e r i e s used  chronoamperometry with a 1-sec  efflux  mesotelencephalic  following periods  To examine t h i s  synthesis,  and  s t r i a t u m , and  DA  catecholamine  d u r i n g a 30-min t e s t  of  copulation.  Method Subjects The  and  Surgery  female and  male Long-Evans r a t s used i n Experiment  were purchased from C h a r l e s previous  experiments.  ovariectomized  The  R i v e r Canada and  housed as  IVa  i n the  females were b i l a t e r a l l y  under sodium p e n t o b a r b i t a l a n e s t h e s i a  one  month  147 prior  to this  experiment.  these  f e m a l e s as i n t h e p r e v i o u s A group of  tests  of  15 m a l e r a t s  sexual behavior  surgery.  All  outlined  Sexual r e c e p t i v i t y  (450 t o  (Page 5 9 ) .  w i t h sodium p e n t o b a r b i t a l  (Somnitol,  assembly c o n s i s t i n g  of  electrode  attached  screw,  electrode  embedded i n c o r t e x ,  indicator  (n = 5 ) ,  electrode  striatum  stereotaxically. with dental and s u r g i c a l  to a s k u l l  acrylic.  for  their  III,  testing currents  test  of  surgery  chamber.  All  during this  Electrochemical  a Ag/AgCl  either  of  for  Paxinos  rats  auxiliary  reference graphite accumbens  implanted  firmly  to  were  the  of  skull  electrodes  identical  MPOA p l a c e m e n t s  and Watson  DA ( n u c l e u s  (MPOA) o x i d a t i o n  i n an e l e c t r i c a l l y  to  and a t h r e e -  the placement  that  10  anesthetized  the nucleus  implantation  except  extracellular  or c a t e c h o l a m i n e  2 days a f t e r  60 m g / k g )  least  experience  and a s t e a r a t e - m o d i f l e d  Coordinates  procedures  sexual  o r MPOA ( n = 5) was  made a c c o r d i n g t o t h e a t l a s  striatum)  for  The a s s e m b l y was a t t a c h e d  t h o s e used i n E x p e r i m e n t  postsurgical  chambers p r i o r  a stainless-steel  aimed a t  (n = 5 ) ,  was g i v e n a t  The m a l e s w e r e  electrode  paste  700 g )  in the b i l e v e l  I  in  experiments.  had a c h i e v e d t h e c r i t e r i a  in Experiment  was i n d u c e d  signals  shielded,  d i s p l a y e d measureable  were  (1982).  accumbens was  to  A and  conducted  Plexiglas oxidation  test.  Measurements  Measurements  of  extracellular  DA o r  concentrations  were o b t a i n e d u s i n g 1-sec  (Lane & B l a h a ,  1986).  Oxidation currents  catecholamine pulse  chronoamperometry  were measured  by  148 applying a potential (vs.  pulse  the Ag/AgCl r e f e r e n c e  of  approximately  electrode)  - 1 0 0 mV t o  and s a m p l e d a t  +250 mV  20-sec  intervals. Behavioral  Testing  The m a l e r a t s electrode shielded  Procedures were t e s t e d  implantation.  Tests  for  were c o n d u c t e d  29 x 29 x 45 cm u n i l e v e l  a wire-mesh  floor  two s i d e s .  Each m a l e was p l a c e d  stable  and w i r e  chronoamperometric  sexual behavior  Plexiglas  screen t h a t  divided  which a s e x u a l l y r e c e p t i v e  other  t h e chamber.  the  female,  between b o t h a n i m a l s .  The m e a s u r e s o f  analyzed  I  after  in Experiment  which the  electrically chamber  with  of  into  t h e chamber. for  at  the  in  introduction  allow physical copulatory  (Page 59) w e r e r e c o r d e d  A  least  f e m a l e was p l a c e d  F i v e min a f t e r  t h e s c r e e n was removed t o  after  t h e chamber  was e s t a b l i s h e d  30 m i n , a f t e r side of  i n an  testing  i n one s i d e  baseline  1 week  the  of  contact  behavior for  30 m i n ,  f e m a l e was r e m o v e d .  Histology Histological was made a f t e r  verification  Experiment  sodium p e n t o b a r b i t o l  were s u b s e q u e n t l y  were c u t ,  All  rats  in the t a r g e t  shown i n F i g u r e s  19,  electrode  frozen  in a cryostat  slides,  and t h e i r  and e x a m i n e d u n d e r  2 0 , and 2 1 .  The e l e c t r o d e  with  brains  solution.  and 40-um  i n e a c h g r o u p had i n d i c a t o r structures.  placements  The m a l e s w e r e a n e s t h e t i z e d  i n a 40% f o r m a l i n / s u c r o s e  m o u n t e d on g l a s s  microscope. ending  IVb.  indicator  (60 m g / k g ) a n d d e c a p i t a t e d ,  were removed and s t o r e d brains  of  The  sections  a  electrodes  placements  are  149  150 Figure  2 0 . E l e c t r o d e placements (n = 5) d i r e c t e d at t h e s t r i a t u m i n Experiment IVa.  . 2  mm  151  152 Statistical  Analyses  The c h r o n o a m p e r o m e t r i c  samples  min p e r i o d p r i o r  to the  into  5 min each.  two b i n s  of  introduction  for  difference  s c o r e s wera e s t a b l i s h e d  rat  each 5 - m i n b i n .  from the  first.  was t h e n c o m p a r e d t o  Difference  event the 2)  its  which the first  first  record  following  the  ejaculation  series  first  second e j a c u l a t i o n  the t h i r d  occurred;  and t h e n e x t  second c o p u l a t o r y  5)  score.  began  occurred;  copulatory  8)  series  values  4)  These e v e n t s  were  3)  6) t h e p o i n t as t h e  and 9 )  (defined  for  the  5 rats  and a n a l y z e d u s i n g a w i t h i n - s u b j e c t s The B o n f e r r o n i  experiment-wise  error  the  first  at which  first  the  intromission  at which  between t h e the point  as t h e  at  at which  between t h e  1)  screen;  the point  the point  the midpoint  began  relevant each  f o l l o w i n g t h e second e j a c u l a t i o n ) .  s c o r e s were t h e n c a l c u l a t e d  measures.  behavior.  7) t h e p o i n t  intromission;  was  each  for  the midpoint  (defined  value  record of  f e m a l e was b e h i n d t h e  intromission;  divided  t h e second 5  nine b e h a v i o r a l l y  occurred;  ejaculation);  and t h e n e x t  intromission  event  for  sexual  w h i c h t h e s c r e e n was r e m o v e d ;  ejaculation  ejaculation  of  10-  chronoamperometric  the chronoamperometric  intromission  during the  f e m a l e were  The c h r o n o a m p e r o m e t r i c  5-min p e r i o d d u r i n g which the at  the  by s u b t r a c t i n g  from the baseline d i f f e r e n c e  the point  of  Baseline  s c o r e s were c a l c u l a t e d  e v e n t s by s u b t r a c t i n g  each r a t  A mean c h r o n o a m p e r o m e t r i c  calculated  min v a l u e  for  the second at  which  first Mean  difference  i n each g r o u p f o r ANOVA f o r  method was used t o c o r r e c t  p r o d u c e d b y a l a r g e number o f  each  repeated the  elevated  repeated  153 measures.  The c o r r e c t e d  (including  the baseline  significant  error  rate  score)  ANOVA, p o s t - h o c  was p_<.005 b e c a u s e  were a n a l y z e d .  comparisons  made u s i n g t h e T u k e y m e t h o d ,  For  10  events  each  among t h e e v e n t s  were  p_<.05.  Results All  15 r a t s  showed an i m m e d i a t e  interest  in the  f e m a l e when she was p l a c e d b e h i n d t h e s c r e e n . marked b y an i m m e d i a t e o r i e n t a t i o n s c r e e n or p r o b i n g t h e i r screen, rats  and e n g a g i n g  tried  snouts  through the openings  female w i t h  attempted to climb the screen. within  20 s o f  the removal of  c o p u l a t i o n during the Nucleus  their  All  rats  of  biting  in  grooming.  was the  the Several  f o r e p a w s and some e v e n initiated  t h e s c r e e n and a l l  copulation  displayed  active  test.  Accumbens  A representative Figure  30-min  interest  toward the screen,  i n extended p e r i o d s  to grab the  This  receptive  chronoamperometric  22A w i t h b e h a v i o r a l  apparent  events  shown i n r e a l  a r e s e v e r a l dynamic changes  particular  elements  t h e DA o x i d a t i o n  of  occurred  in this  f e m a l e was p l a c e d b e h i n d t h e s c r e e n . back t o b a s e l i n e  is depicted time.  i n DA e f f l u x  sexual behavior.  signal  record  Readily  associated  the  increase  rat  receptive  when t h e  The s i g n a l  b e f o r e t h e s c r e e n was r e m o v e d .  first  maintained u n t i l  copulatory  the r a t  series.  with  An i m m e d i a t e  began t o A  This  increase  achieved e j a c u l a t i o n .  in  drift  further  i n c r e a s e was o b s e r v e d when t h e s c r e e n was removed and t h e initiated  in  Each  rat  was ejaculation  154  F i g u r e 22.  Changes i n DA o x i d a t i o n c u r r e n t i n the nucleus accumbens d u r i n g phases of s e x u a l behavior i n Experiment IVa. A: A r e p r e s e n t a t i v e chronoamperom e t r i c r e c o r d from a s i n g l e male r a t . Symbols: I = i n t r o m i s s i o n ; E = e j a c u l a t i o n . B: Changes i n DA o x i d a t i o n c u r r e n t i n the nucleus accumbens (n = 5) d u r i n g phases of s e x u a l behavior i n Experiment IVa. Values a r e means + SE. Symbols: FEM IN, female i n chamber behind the s c r e e n ; SCR OUT, s c r e e n removed t o permit c o n t a c t between the male and female; 1-1, f i r s t i n t r o m i s s i o n of the f i r s t c o p u l a t o r y s e r i e s ; E - l , f i r s t e j a c u l a t i o n ; PEI-1, midpoint of the f i r s t p o s t e j a c u l a t o r y i n t e r v a l ; 1-2, f i r s t i n t r o m i s s i o n of the second c o p u l a t o r y s e r i e s ; E-2, second e j a c u l a t i o n ; PEI-2, midpoint of second p o s t e j a c u l a t o r y i n t e r v a l ; 1-3, f i r s t i n t r o m i s s i o n of the third copulatory series. Chronoamperometric r e c o r d s were o b t a i n e d from a s t e a r a t e - m o d i f i e d carbon paste e l e c t r o d e with a 20-sec sampling r a t e . Current v a l u e s r e p r e s e n t the sum of both background c u r r e n t and DA o x i d a t i o n c u r r e n t . * * p_<.05, * p_<.01, from the b a s e l i n e d i f f e r e n c e s c o r e .  NUCLEUS ACCUMBENS  155  156 was f o l l o w e d the signal  by a r e d u c t i o n  rose before  A similar  the  signal  min p e r i o d t h a t DA o x i d a t i o n  the  four  signals  mean d i f f e r e n c e  for  that  scores depicted  the midpoints  effect  Post-hoc  different for  for  score;  f r o m one a n o t h e r ,  lower  those  scores, each  toward  o f DA by  the  significantly the  and t h e  next  than the other  a l t h o u g h t h e y were n o t  got smaller  the  score  however,  the magnitude of  each i n t r o m i s s i o n  pattern  The ANOVA  of  5-  increase  22b.  s c o r e s were  between each e j a c u l a t i o n  to note t h a t ,  did not  the  the  back  shown c l e a r l y  comparisons  the difference  were s i g n i f i c a n t l y  interesting  scores  of  overall  is  in  Although  The o v e r a l l  in Figure  than the baseline d i f f e r e n c e  intromission is  all  during  began t o d r i f t  during sexual behavior  F ( 9 , 3 6 ) = 6 . 1 1 , p_<.0001.  higher  nA, r e s p e c t i v e l y )  t h o s e two r a t s  rats,  mean i n c r e a s e s  5-min p e r i o d the s i g n a l s  detected a s i g n i f i c a n t  revealed  four  f e m a l e was b e h i n d t h e s c r e e n . of  however,  copulation.  in the other  when t h e s c r e e n was r e m o v e d .  oxidation  of  showed much l a r g e r  ( 3 . 4 and 6 . 2  signals  baseline during the further  each r e i n i t i a t i o n  p a t t e r n was o b s e r v e d  a l t h o u g h two of DA o x i d a t i o n  i n t h e DA o x i d a t i o n s i g n a l ,  the  scores  scores.  It  significantly  difference  as t h e t e s t  progressed.  Strlatum A representative Figure  chronoamperometric  23a w i t h b e h a v i o r a l  i n t h e DA o x i d a t i o n s i g n a l no b e h a v i o r a l fall  event  events  in real  record  is depicted  in  time.  A gradual  rise  was o b s e r v e d t h r o u g h o u t  was c o n s i s t e n t l y  i n t h e DA o x i d a t i o n s i g n a l .  associated  The s i g n a l  the t e s t ,  with a rise  d i d not  rise  but or  during  157  F i g u r e 23.  Changes i n DA o x i d a t i o n c u r r e n t i n the s t r i a t u m d u r i n g phases of sexual behavior i n Experiment IVa. A: A r e p r e s e n t a t i v e chronoamperometric record from a s i n g l e male r a t . Symbols: I = i n t r o m i s s i o n ; E = ejaculation. B: Changes i n DA o x i d a t i o n i n the s t r i a t u m (n = 5) d u r i n g phases of sexual behavior i n Experiment IVa. Values a r e means + SE. Symbols: FEM IN, female i n chamber behind the screen; SCR OUT, screen removed to permit c o n t a c t between the male and female; 1-1, f i r s t i n t r o m i s s i o n of the f i r s t c o p u l a t o r y s e r i e s ; E - l , f i r s t e j a c u l a t i o n ; PEI-1, midpoint between the f i r s t p o s t e j a c u l a t o r y i n t e r v a l ; 1-2, f i r s t i n t r o m i s s i o n of the second c o p u l a t o r y s e r i e s ; E-2, second e j a c u l a t i o n ; PEI-2, midpoint between the second p o s t e j a c u l a t o r y i n t e r v a l ; 1-3, f i r s t i n t r o m i s s i o n of the t h i r d c o p u l a t o r y s e r i e s . Chronoamperometric records were obtained from a s t e a r a t e - m o d i f i e d carbon paste e l e c t r o d e with a 20sec sampling r a t e . Current values represent the sum of both background c u r r e n t and DA o x i d a t i o n c u r r e n t . * * p_<.05, * p_<.01, from the b a s e l i n e d i f f e r e n c e s c o r e .  159 the rise  5-min p e r i o d  with the  female behind the screen,  appreciably during the A similar  observed pattern 22b.  gradual  in the other  first  incline four  rats  during the t e s t .  scores,  a significant  F ( 9 , 3 6 ) - 6 . 1 7 , p_<.0001.  score revealed t h a t significantly  f r o m the  ejaculation.  None o f  different  the subsequent  w h i c h was s i g n i f i c a n t l y  except  in  for of  score u n t i l  s c o r e s were  the score  for  DA e f f l u x  events  efflux  observed  for  increase  in the catecholamine  those  elevated the  midpoint series,  9 scores.  record  is depicted  was s t r i k i n g l y  time. similar  i n t h e n u c l e u s accumbens. oxidation signal  before  An  first  to  followed  by a d e c r e a s e  The s i g n a l  immediate  began t o A  however,  the signal  Similar  rose before  patterns  of  oxidation  each r e i n i t i a t i o n  catecholamine  the  drift  further  Each e j a c u l a t i o n  in the catecholamine  that  o c c u r r e d when  t h e s c r e e n was r e m o v e d .  copulatory series.  in  The  i n c r e a s e was o b s e r v e d when t h e s c r e e n was removed and t h e the  first  significantly the  shown i n r e a l  f e m a l e was p l a c e d b e h i n d t h e s c r e e n .  initiated  Figure  each  copulatory  than the other  chronoamperometric  catecholamine  back t o b a s e l i n e  overall  s c o r e s were n o t  and t h e t h i r d  greater  24a w i t h b e h a v i o r a l of  effect  was  Area  A representative  pattern  This  Post-hoc comparisons  between t h e second e j a c u l a t i o n  Medial Preoptic  overall  baseline difference  f r o m one a n o t h e r  signal  scores depicted  t h e mean d i f f e r e n c e  it  series.  i n t h e OA o x i d a t i o n  i s shown b y t h e mean d i f f e r e n c e  The ANOVA d e t e c t e d  Figure  copulatory  nor d i d  of  rat was  signal, copulation.  o x i d a t i o n were o b s e r v e d  in  160  F i g u r e 24.  Changes i n catecholamine o x i d a t i o n c u r r e n t i n the medial p r e o p t i c area d u r i n g phases of s e x u a l behavior i n Experiment IVa. A: A r e p r e s e n t a t i v e chronoamperometr i c r e c o r d from a s i n g l e r a t . Symbols: I = i n t r o m i s s i o n ; E = e j a c u l a t i o n . B: Changes i n o x i d a t i o n c u r r e n t i n the medial p r e o p t i c area (n = 5) d u r i n g phases of s e x u a l behavior i n Experiment IVa. Values are means + SE. Symbols: FEM IN, female i n behind the s c r e e n ; SCR OUT, s c r e e n removed t o permit c o n t a c t between the male and female; 1-1, f i r s t i n t r o m i s s i o n of the f i r s t c o p u l a t o r y s e r i e s ; E - l , f i r s t e j a c u l a t i o n ; PEI-1, midpoint between the f i r s t p o s t e j a c u l a t o r y i n t e r v a l ; 1-2, f i r s t i n t r o m i s s i o n of the second c o p u l a t o r y s e r i e s ; E-2; second e j a c u l a t i o n ; PEI-2, midpoint between the second p o s t e j a c u l a t o r y i n t e r v a l ; 1-3, f i r s t i n t r o m i s s i o n of the t h i r d c o p u l a t o r y s e r i e s . Chronoamperometric r e c o r d s were obtained from a s t e a r a t e - m o d i f i e d carbon paste e l e c t r o d e with a 20-sec sampling r a t e . Current v a l u e s r e p r e s e n t the sum of both background c u r r e n t and DA o x i d a t i o n c u r r e n t . * * p_<.05, * pjC.CLl, from the b a s e l i n e d i f f e r e n c e s c o r e .  MEDIAL PREOPTIC AREA  FEM. IN  SCR. OUT  1-1  E-1  PB-1  1-2  E-2  PB-2  1-3  162 the other  four r a t s .  This o v e r a l l pattern  d i f f e r e n c e scores depicted  i n Figure  24b.  i s shown by the mean Although the magnitude  of the catecholamine o x i d a t i o n s i g n a l s was g e n e r a l l y s m a l l e r t h a t observed f o r DA o x i d a t i o n s i g n a l s i n the nucleus the ANOVA d e t e c t e d F( 9, 36 ) =25 .68, revealed  a significant effect  p_<.0001.  f o r those  scores,  with  score  except t h e midpoints between  e j a c u l a t i o n and subsequent r e i n i t i a t i o n of c o p u l a t i o n elevated  accumbens,  Post-hoc comparisons of each  that a l l d i f f e r e n c e scores  than  were  s i g n i f i c a n t l y from the b a s e l i n e d i f f e r e n c e s c o r e .  As  the nucleus accumbens, a l t h o u g h these s c o r e s d i d not d i f f e r  s i g n i f i c a n t l y from one another, the magnitude of the d i f f e r e n c e scores  f o r each i n t r o m i s s i o n got s m a l l e r  as the t e s t  progressed.  Discussion T h i s experiment p r o v i d e s  the f i r s t  demonstration t h a t DA  efflux  i n the nucleus accumbens and s t r i a t u m , and catecholamine  efflux  i n the MPOA, i n c r e a s e s  behavior. differed  i n male r a t s d u r i n g  sexual  However, t h e p a t t e r n and magnitude of the i n c r e a s e among these r e g i o n s .  oxidation s i g n a l s increased was p l a c e d  In the nucleus accumbens, DA  immediately when a r e c e p t i v e  behind the s c r e e n .  maintained throughout the f i r s t  The e l e v a t e d copulatory  s i g n a l s were series.  Although  those s i g n a l s decreased a f t e r each e j a c u l a t i o n , they were elevated  s i g n i f i c a n t l y above b a s e l i n e v a l u e s .  of c o p u l a t i o n was preceded by a r i s e  female  Each  still  reinitiation  i n the DA o x i d a t i o n s i g n a l s ,  however, t h e magnitude of the mean DA o x i d a t i o n s i g n a l s t h a t  163 c o i n c i d e d with  the beginning  p r o g r e s s i v e l y smaller  of each c o p u l a t o r y  s e r i e s got  throughout the 30-min t e s t of c o p u l a t i o n .  In c o n t r a s t , the DA o x i d a t i o n s i g n a l s i n the s t r i a t u m were not a f f e c t e d by t h e placement of a r e c e p t i v e female behind the screen.  However, those s i g n a l s i n c r e a s e d g r a d u a l l y  throughout  the t e s t but d i d not correspond t o any p a r t i c u l a r aspect of sexual  behavior.  MPOA r e v e a l e d  F i n a l l y , catecholamine o x i d a t i o n s i g n a l s i n the  a s m a l l e r , but e s s e n t i a l l y i d e n t i c a l , p a t t e r n t o  t h a t observed f o r DA o x i d a t i o n s i g n a l s i n the nucleus Together, these r e s u l t s c o n f i r m  earlier  ex v i v o demonstrations  t h a t DA s y n t h e s i s , r e l e a s e , or u t i l i z a t i o n copulation al.,  (Ahlenius  accumbens.  increase  during  e t a l . , 1987; Hoffman e t a l . , 1987; Mas e t  1987). The r e s u l t s of Experiment IVa a r e c o n s i s t e n t with  i n Experiment I I I t h a t DA t e r m i n a l s  evidence  i n the nucleus accumbens and  MPOA form p a r t of the n e u r a l b a s i s of a n t i c i p a t o r y s e x u a l motivation increased  i n male r a t s .  Oxidation  s i g n a l s i n both  immediately and d r a m a t i c a l l y upon p r e s e n t a t i o n  r e c e p t i v e female behind the s c r e e n ,  a s s o c i a t e d with  the p r e s e n t a t i o n  i n the MPOA i s  of a n a t u r a l s e x u a l  In most r a t s t h e r e was a f u r t h e r i n c r e a s e s i g n a l s when the s c r e e n  was removed.  preceded by an i n c r e a s e  incentive.  i n the o x i d a t i o n  S i m i l a r l y , an i n c r e a s e i n  the o x i d a t i o n s i g n a l s preceded each r e i n i t i a t i o n i n d i c a t e s t h a t the i n i t i a t i o n  of a  i n d i c a t i n g t h a t DA e f f l u x i n  the nucleus accumbens and catecholamine e f f l u x  This  regions  of c o p u l a t i o n .  of a c o p u l a t o r y  series i s  i n DA or catecholamine e f f l u x  i n these  regions.  Although t h i s  III that h a l o p e r i d o l latencies,  i s c o n s i s t e n t with evidence i n Experiment  i n f u s i o n s t o t h e MPOA i n c r e a s e d  intromission  i t i s not e n t i r e l y c o n s i s t e n t with t h e lack of e f f e c t  of h a l o p e r i d o l i n f u s i o n s t o t h e nucleus accumbens on mount or intromission  latencies.  I t i s p o s s i b l e , however, t h a t the r i s e  i n DA e f f l u x  i n t h e nucleus accumbens t h a t precedes t h e  i n i t i a t i o n of c o p u l a t i o n  i s an epiphenomenon of MPOA a c t i v a t i o n .  As mentioned p r e v i o u s l y , the MPOA sends a f f e r e n t s t o DA c e l l bodies i n the VTA v i a the medial f o r e b r a i n bundle. these a f f e r e n t s c o u l d  lead to increased  DA r e l e a s e  A c t i v a t i o n of i n t h e nucleus  accumbens. The  l a c k of an i n c r e a s e  presentation the s c r e e n  the p o i n t a t which  was removed, and t h e p o i n t a t which the f i r s t  involved  suggests that DA e f f l u x  i n a n t i c i p a t o r y sexual  of c o p u l a t i o n .  This  motivation  i n the s t r i a t u m i s or t h e i n i t i a t i o n  i s c o n s i s t e n t with evidence i n Experiment  I I I t h a t antagonism of DA t e r m i n a l s affect  DA e f f l u x d u r i n g t h e  of the female behind the s c r e e n ,  intromission occurred, not  in striatal  i n the s t r i a t u m does not  l e v e l changing or the i n i t i a t i o n of mounts or  intromissions.  However, s i m i l a r t o the resul.ts of Experiment  I I I , these data a r e not c o n s i s t e n t with p r e v i o u s electrolytic  reports  that  l e s i o n s of the s u b s t a n t i a n i g r a pars compacta  source of DA p r o j e c t i o n s t o the s t r i a t u m )  i n c r e a s e mount and  i n t r o m i s s i o n l a t e n c i e s (Mcintosh & B a r f i e l d , the number of e j a c u l a t i o n s  (Brackett  would appear t h a t DA d e p l e t i o n  (the  1984) or decrease  e t a l . , 1986).  i n the s t r i a t u m  Thus,  it  i s not s u f f i c i e n t  165 to d i s r u p t t h e i n i t i a t i o n of c o p u l a t i o n  or decrease the number of  ejaculations. In c o n t r a s t , t h e p r o g r e s s i v e throughout the c o p u l a t o r y may  rise  i n the s t r i a t a l  t e s t suggests t h a t s t r i a t a l  c o n t r i b u t e t o c e r t a i n e f f e c t s observed  copulation.  I t i s tempting t o s p e c u l a t e  s t r i a t a l DA r e l e a s e serve male r a t engages  DA s i g n a l DA r e l e a s e  i n t h e l a t e r phases of  that  increases i n  t o suppress e j a c u l a t o r y mechanisms as a  i n m u l t i p l e e j a c u l a t i o n s , e s p e c i a l l y i n l i g h t of  evidence i n Experiment I I I t h a t h a l o p e r i d o l i n f u s i o n s t o t h e striatum  increase  suggestion dependent  t h e t o t a l number of e j a c u l a t i o n s .  c o u l d be t e s t e d  This  f o r m a l l y u s i n g p e n i l e r e f l e x e s as t h e  measure.  EXPERIMENT IVb The r e s u l t s of Experiment IVa suggest t h a t DA e f f l u x nucleus accumbens and catecholamine e f f l u x associated  with the p r e s e n t a t i o n  male r a t s . evaluated  consideration  of a n a t u r a l s e x u a l  t h i s suggestion  i s t h e s p e c i f i c i t y of t h e e l i c i t i n g  regardless  to i n c r e a s e  of i t s s e x u a l  i n c e n t i v e to  need t o be  can be accepted;  i s p o s s i b l e t h a t merely p r e s e n t i n g screen,  i n t h e MPOA a r e  However, s e v e r a l c o n t r o l c o n d i t i o n s before  i n the  An important stimulus.  It  a c o n s p e c i f i c behind t h e  incentive value,  i s sufficient  DA and catecholamine o x i d a t i o n s i g n a l s i n the nucleus  accumbens and MPOA, r e s p e c t i v e l y . p o s s i b i l i t y by a n a l y z i n g  Experiment IVb examined  oxidation currents  i n males  with e i t h e r another male, a s e x u a l l y n o n r e c e p t i v e  this  presented  female, a s l i d e  166 smeared with e s t r o u s v a g i n a l s e c r e t i o n s , or a r e c e p t i v e  female  behind the s c r e e n .  Method S u b j e c t s and  Stimuli  The 15 males used i n Experiment this. all  IVa were used as s u b j e c t s i n  D e t a i l s of t h e i r s u r g e r y and the housing c o n d i t i o n s f o r  animals can be found i n Experiment  females used i n Experiment  IVa (Page 147).  IVa were used as s e x u a l l y  s t i m u l u s females i n t h i s experiment.  The  receptive  Sexual r e c e p t i v i t y  was  induced as i n the p r e v i o u s experiments, and these females were presented t o the males a p p r o x i m a t e l y 5 h a f t e r p r o g e s t e r o n e administration.  A group of 6 o v a r i e c t o m i z e d females t h a t had not  r e c e i v e d e s t r o g e n or p r o g e s t e r o n e treatment f o r at l e a s t  4 months  p r i o r to t h i s experiment were used as s e x u a l l y n o n r e c e p t i v e female c o n s p e c i f i c s .  A group of 6 i n t a c t , s e x u a l l y a c t i v e males  were used as male c o n s p e c i f i c s .  E s t r o u s v a g i n a l s e c r e t i o n s were  taken from s e x u a l l y r e c e p t i v e females by swabbing the v a g i n a g e n t l y with a c o t t o n - t i p p e d a p p l i c a t o r dampened with d i s t i l l e d water.  These s e c r e t i o n s were a p p l i e d t o a microscope s l i d e  presented  and  immediately to the males by p l a c i n g the s l i d e a d j a c e n t  to the s c r e e n . E l e c t r o c h e m i c a l Measurements Measurement of e x t r a c e l l u l a r  DA or catecholamine  c o n c e n t r a t i o n s were made as i n Experiment chronoamperometry.  IVa u s i n g 1-sec p u l s e  167 Behavioral  Testing  Procedures  T e s t s were c o n d u c t e d electrically  shielded Plexiglas  As i n E x p e r i m e n t established stimuli  IVa, a stable  i n each m a l e f o r  for  presentation  of  smeared w i t h receptive  that  each s t i m u l u s . the male,  estrous  female.  This  smaller  of  receptive  female.  All  of  which  Each s t i m u l u s  males r e c e i v e d  the was  t h e same  female,  the  and f i n a l l y  stimulus  e.g.,  salience.  larger  It  was  would not  salience,  the presentation  of  Experiment  30 m i n .  IVa.  the  the present  experiment.  Statistical  Analysis  Baseline  chronoamperometric  d e t e r m i n e d as i n E x p e r i m e n t calculated  analyses  of be  e.g.,  IVa.  Difference  from the chronoamperometric  each 5-min p e r i o d t h a t the presentation  of  the s t i m u l i  scores scores  record of  the receptive  female  to of  following  were were  each r a t  were p r e s e n t e d ,  the  receptive  were p e r f o r m e d  difference  to  hoped  T h i s was done t o c o n f i r m t h e r e s u l t s  Histological  order  the  produced by s t i m u l i the male,  the  slide  t h e s c r e e n was removed and t h e m a l e s w e r e a l l o w e d for  was  p r e s e n t a t i o n was b e l i e v e d  potentially  Following  experiment.  baseline  30 m i n , a f t e r  same  A 20-min p e r i o d separated  current  salience,  overshadowed by t h o s e o f  for  least  secretions,  order  an a s c e n d i n g o r d e r  potentially  copulate  used i n t h a t  the nonreceptive  vaginal  IVa i n the  chronoamperometric  at  any change i n o x i d a t i o n  female,  chamber  5 m i n , then removed.  presentation:  reflect  Experiment  were p r e s e n t e d b e h i n d t h e s c r e e n .  presented  of  4 days a f t e r  for  as was done  i n Experiment  IVa.  168 Mean d i f f e r e n c e  s c o r e s were c a l c u l a t e d  group f o r  each s t i m u l u s  ANOVA f o r  repeated measures.  correct large  for  analyzed.  For  The B o n f e r r o n i  experiment-wise  repeated measures.  p_<.01 b e c a u s e 5 e v e n t s  the  and a n a l y z e d u s i n g a  the elevated  number o f  for  (including  each s i g n i f i c a n t  made u s i n g t h e T u k e y m e t h o d ,  5 rats  in  each  within-subjects method was used  error  produced by a  The c o r r e c t e d the baseline  to  error  score)  ANOVA, p o s t - h o c  rate  was  were  comparisons  were  p_<.05.  Results A gradual  increase  when t h e s t i m u l i  to  it,  t h e w i r e mesh. the s l i d e of  All  but  smeared w i t h  stimuli.  the r e c e p t i v e  attention  one o f estrous  female,  snouts  i n each male Typically,  toward the screen,  vaginal  however,  secretions.  IVa, a l l  accumbens e l e c t r o d e s ;  2 with  lick  than  males a t t e m p t e d  female through the screen w i t h t h e i r  in  Presentation  e v o k e d more i n t e r e s t  and 1 w i t h MPOA e l e c t r o d e s )  move  through the openings  t h e males were o b s e r v e d t o  As i n E x p e r i m e n t  some (2 w i t h n u c l e u s electrodes;  their  and p r o b e t h e i r  the receptive  other  was o b s e r v e d  were p r e s e n t e d b e h i n d t h e s c r e e n .  t h e males would d i r e c t adjacent  in a c t i v i t y  the  to  forepaws  grab and  striatal  attempted to climb  the  screen. Nucleus All  Accumbens m a l e s showed i m m e d i a t e  when each s t i m u l u s  increases  was p r e s e n t e d .  i n c r e a s e d t h e DA o x i d a t i o n s i g n a l s  i n DA o x i d a t i o n  Although a l l  of  over b a s e l i n e ,  the  signals  stimuli  presentation  of  169 the r e c e p t i v e clearly  f e m a l e had t h e  largest  b y t h e mean d i f f e r e n c e  (Panel A ) .  F(4,16)=8.33,  a significant  pjC.001.  score revealed that  t h e y were a l l  baseline difference  score,  the presentation  the receptive  greater  of  than the scores  nonreceptive  female,  secretions.  Interestingly,  during the presentation largest  difference  of  scores  Experiment  signals  IVa  virtually  (data not  of  than  each the  score  for  All  the  vaginal  climbed the  female d i d  event.  of  the male,  estrous  t h e two m a l e s t h a t  this  greater  for  significantly  containing  when t h e s c r e e n was r e m o v e d , and a l l DA o x i d a t i o n  comparisons  f e m a l e was  the receptive  25  effect  t h e mean d i f f e r e n c e  the presentation  for  shown  in Figure  significantly  and t h e s l i d e  is  overall  Post-hoc  however,  for  This  scores depicted  The ANOVA d e t e c t e d  these scores,  effect.  screen  n o t have  males  the  copulated  showed a d y n a m i c p a t t e r n  identical  to  those observed  of  in  shown).  Str iatum None o f appreciably. depicted  the s t i m u l i This  in Figure  significant  effect  is  i n c r e a s e d t h e DA o x i d a t i o n  shown by t h e mean d i f f e r e n c e  25 ( P a n e l B ) . for  signals scores  The ANOVA d i d n o t d e t e c t  these scores,  F ( 4 , 1 6 ) =0 . 9 4 , p_>.35.  m a l e s c o p u l a t e d when t h e s c r e e n was removed a n d , as i n IVa,  all  signals  showed a p r o g r e s s i v e throughout  Medial Preoptic All oxidation  the t e s t  increase  (data not  signals  when t h e s l i d e  All  Experiment  i n t h e DA o x i d a t i o n shown).  Area  m a l e s showed i m m e d i a t e  a  \ increases  in  catecholamine  or t h e r e c e p t i v e  female  was  170  Figure  25.  Changes i n DA o x i d a t i o n c u r r e n t f r o m b a s e l i n e i n t h e n u c l e u s accumbens ( n = 5) and s t r i a t u m ( n = 5 ) , and mean c h a n g e s i n c a t e c h o l a m i n e o x i d a t i o n c u r r e n t i n t h e m e d i a l p r e o p t i c a r e a (n = 5 ) , observed d u r i n g a 5 - m i n t e s t i n w h i c h e i t h e r a m a l e r a t (MALE), a n o n r e c e p t i v e f e m a l e (NR FEM), a g l a s s s l i d e c o n t a i n i n g e s t r o u s v a g i n a l s e c r e t i o n s ( S L I D E ) , or a r e c e p t i v e f e m a l e (R FEM) was p l a c e d b e h i n d a w i r e mesh s c r e e n i n t h e same chamber as t h e e x p e r i m e n t a l male r a t . V a l u e s a r e means + SE. * p_<.05,  * p_<.01,  from the baseline d i f f e r e n c e  score.  NUCLEUS ACCUMBENS  *  STRIATUM s  -i  I  MALE  NR FEM  SUD€  R FEM  MEDIAL PREOPTIC AREA  MALE  NR FEM  SUOE  R FEM  MALE  NR FEM  SLIDE  R FEM  presented. increase  In contrast,  in Figure  This  i s shown by t h e mean d i f f e r e n c e  25 ( P a n e l C ) .  for  The ANOVA d e t e c t e d  these scores,  comparisons  of  nonreceptive over  signals  each s c o r e r e v e a l e d t h a t  female  score,  female d i d .  the receptive  f e m a l e was g r e a t e r  two s c o r e s were n o t  for  of the r e c e p t i v e  this  than the next was r e m o v e d , oxidation  event;  and a l l  IVa  score.  than t h a t  for  different  virtually  the s l i d e ,  f r o m one  All  these  the  difference  s c o r e was o n l y 0 . 1 nA  m a l e s c o p u l a t e d when t h e  identical  for  another.  largest  of  and  score  climbed the screen during  this  the  significantly  whereas b o t h t h e s l i d e  showed a d y n a m i c p a t t e r n  (data not  t h e male nor  scores  f e m a l e had t h e  however,  highest  signals  Experiment  group t h a t  overall  Post-hoc  A l t h o u g h t h e mean d i f f e r e n c e  significantly  The one male i n t h i s presentation  neither  not  depicted  a significant  increased the d i f f e r e n c e  the baseline d i f f e r e n c e  did  f e m a l e was  scores  F( 4 , 1 6 ) =19 . 2 6 , p_<.0001.  the receptive  score  oxidation  a p p r e c i a b l y when t h e male o r t h e n o n r e c e p t i v e  presented.  effect  catecholamine  larger screen  catecholamine  t o those observed  in  shown).  Discussion Experiment Experiment  IVb r e p l i c a t e s  I V a by d e m o n s t r a t i n g t h a t  DA and c a t e c h o l a m i n e  oxidation  and MPOA o f m a l e r a t s , the presentation however,  and e x t e n d s t h e r e s u l t s  of  the pattern  of  signals  respectively,  a sexual the  the  increases  in the nucleus  are r e l a t i v e l y  Incentive. increases  immediate  of  accumbens  specific  As i n E x p e r i m e n t  differed  in  among t h e s e  to  IVa, two  173 regions.  Although s m a l l but s i g n i f i c a n t e l e v a t i o n s i n DA  o x i d a t i o n s i g n a l s were observed i n t h e nucleus accumbens the p r e s e n t a t i o n smeared with  of a male, a n o n r e c e p t i v e  estrous  female, or a s l i d e  vaginal s e c r e t i o n s , the presentation  s e x u a l l y r e c e p t i v e female produced a much l a r g e r r i s e oxidation signals.  during  In c o n t r a s t , t h e p r e s e n t a t i o n  male or n o n r e c e p t i v e  of a  i n DA  of e i t h e r a  female d i d not s i g n i f i c a n t l y  increase  catecholamine o x i d a t i o n s i g n a l s i n t h e MPOA, whereas t h e presentation Consistent  of e i t h e r t h e s l i d e or t h e r e c e p t i v e female d i d .  with  t h e r e s u l t s of Experiment IVa,  none of t h e  s t i m u l i a f f e c t e d DA o x i d a t i o n s i g n a l s i n the s t r i a t u m . Although t h e presence of a s e x u a l l y r e c e p t i v e female i s a p a r t i c u l a r l y s a l i e n t stimulus efflux  f o r evoking an i n c r e a s e  i n DA  i n t h e nucleus accumbens, t h e r e l a t i v e l y s m a l l e r but  significant  increases  presentation  i n DA o x i d a t i o n s i g n a l s d u r i n g the  of t h e male, t h e n o n r e c e p t i v e  female, or the s l i d e ,  suggest t h a t DA r e l e a s e i n t h i s s t r u c t u r e may p l a y a g e n e r a l  role  in processing  with  previous  i n c e n t i v e cues.  hypotheses c o n c e r n i n g  i n behavior  (e.g, Crow, 1973;  & Phillips,  1976).  Previous metabolites questioned  This suggestion  i sconsistent  the r o l e of mesolimbic DA systems Fibiger & Phillips,  1986; Mogenson  s t u d i e s t h a t have examined l e v e l s of DA or i t s  ex v i v o f o l l o w i n g p e r i o d s  of c o p u l a t i o n have  t h e s p e c i f i c i t y of DA s y n t h e s i s or r e l e a s e  s t r i a t u m or MPOA t o c o p u l a t o r y  behavior.  Ahlenius  demonstrated t h a t 10 min of c o p u l a t i o n i n c r e a s e d  i n the  e t a l . (1987)  DOPA s y n t h e s i s  174 in both the nucleus  accumbens and s t r i a t u m .  treadmill  locomotion also  increased  striatum,  suggesting  motor  increase  catecholamine  n u c l e u s accumbens. that  that  Similarly,  increased  lengthy bouts  release  utilization  but not  General Experiments  IVa or  inconsistent activity  locomotor  with the  of  of  of  stimuli,  the other  level  of  the  the r e c e p t i v e  behavioral  oxidation signals female. that  activity  several  increases  behavioral did not  during  during the presentation  in this  group,  of  the  were l e s s  the  obvious  scores  presentation  of  increases  DA  receptive  of  accumbens  the  receptive  than those  males w i t h  of  such  the r e c e p t i v e  in  the  individual  which d i d not d i s p l a y of  motor Although  in the nucleus  The p r e s e n t a t i o n  despite  Finally,  that  in  between  and t h e m a g n i t u d e o f  scores  are  i n DA e f f l u x .  and a t t e n t i v e  increase the difference  excitation.  either  female than d u r i n g the  excitation  excitation.  in the s t r i a t u m ,  in  increases  climbed the screen during the presentation  males  i n t h e MPOA,  observations  nonspecific  The two m a l e s w i t h e l e c t r o d e s  the other  yoked  i n c r e a s e d DA  t h e r e was no o b v i o u s r e l a t i o n  f e m a l e had mean d i f f e r e n c e  the  demonstrated  DOPAC l e v e l s  was n o t r e c o r d e d  t h e m a l e s a p p e a r e d more e x c i t e d presentation  motor  however,  for  (1987)  to  i n t h e MPOA.  idea t h a t  could account  the  e x h a u s t i o n and w h e e l r u n n i n g  activity  IVb;  in  i n the s t r i a t u m but not  DA b u t n o t  suggesting that  forced  a l o n e was s u f f i c i e n t  Hoffman e t a l .  both copulation to sexual  t o such c o p u l a t i o n  DOPA s y n t h e s i s  activity  synthesis  However,  female  electrodes  behavioral  a l t h o u g h t h e one male i n t h e MPOA g r o u p  t h a t climbed  t h e s c r e e n d u r i n g the p r e s e n t a t i o n of t h e r e c e p t i v e  female had t h e h i g h e s t mean d i f f e r e n c e s c o r e , higher  than the next h i g h e s t  It i s impossible DA  efflux  efflux  score.  t o r u l e out a g e n e r a l  i n t h e nucleus  i t was o n l y 0.1 nA  locomotor e f f e c t on  accumbens and s t r i a t u m , or c a t e c h o l a m i n e  i n t h e MPOA, d e s p i t e t h e l a c k of obvious evidence i n  Experiments IVa or IVb. appropriate behavior.  However, i t i s d i f f i c u l t  t o d e s i g n an  c o n t r o l f o r t h e locomotor e f f e c t s of c o p u l a t o r y Although t h e yoked c o n t r o l used by Hoffman e t a l .  (1987).was perhaps t h e best attempt t o equate t h e amount of time i n f o r c e d a c t i v i t y with t h e amount of time i n c o p u l a t i o n , i t d i d not p r o v i d e  an adequate c o n t r o l f o r t h e type  of motor  engaged i n d u r i n g c o p u l a t i o n , nor d i d i t c o m p l e t e l y  equate t h e  total  amount of time each r a t was engaged i n motor  e.g.,  the wheel d i d not stop d u r i n g each yoked r a t ' s  inter intromission Interval. catecholamine e f f l u x  i n these  Nevertheless,  a study  regions during  activity  activity,  of DA or  forced  activity  needs t o be conducted b e f o r e t h e s e x u a l s p e c i f i c i t y of t h e present  r e s u l t s can be accepted.  EXPERIMENT IVc Experiments IVa and IVb p r o v i d e changes i n DA or catecholamine e f f l u x  evidence  f o r s e v e r a l dynamic  i n t h e nucleus  accumbens,  s t r i a t u m , or MPOA d u r i n g a n t i c i p a t o r y and consummatory a s p e c t s of s e x u a l behavior  i n t h e male r a t .  female r a t behind  a screen  Placing a sexually receptive  produced an immediate i n c r e a s e i n DA  or catecholamine e f f l u x respectively. increase  i n the nucleus accumbens and MPOA,  The i n i t i a t i o n  of c o p u l a t i o n produced a f u r t h e r  i n most of these r a t s , whereas e j a c u l a t i o n was f o l l o w e d  immediately by a decrease i n DA or catecholamine o x i d a t i o n signals  i n every r a t .  Each r e i n i t i a t i o n  preceded by an i n c r e a s e  of c o p u l a t i o n was  i n the oxidation s i g n a l s .  placement of a r e c e p t i v e female behind t h e s c r e e n  In c o n t r a s t , had no e f f e c t  on DA o x i d a t i o n s i g n a l s i n t h e s t r i a t u m ; however, t h e r e was a progressive copulatory aspect  increase  i n t h e o x i d a t i o n s i g n a l s d u r i n g the  t e s t t h a t was not a s s o c i a t e d with any p a r t i c u l a r  of c o p u l a t o r y  activity.  demonstrated t h a t t h e i n i t i a l  Although Experiment IVb increase  i n DA or c a t e c h o l a m i n e  o x i d a t i o n s i g n a l s l n t h e nucleus accumbens or MPOA was r e l a t i v e l y s p e c i f i c to the presentation  of a s e x u a l  incentive, neither  experiment r u l e d out the p o s s i b i l i t y t h a t g o a l - d i r e c t e d a c t i v i t y , r a t h e r than s e n s o r y p r o c e s s i n g increased  locomotor  of i n c e n t i v e cues  alone,  t h e o x i d a t i o n s i g n a l s i n each of t h e areas.  Another p o t e n t i a l problem i n i n t e r p r e t i n g t h e r e s u l t s of Experiments IVa and IVb stems from the c o n t r o v e r s i a l nature of the s t e a r a t e - m o d i f i e d  e l e c t r o d e used i n those experiments.  As  noted above, s e v e r a l e l e c t r o a c t i v e substances a r e o x i d i z e d a t the same p o t e n t i a l as DA.  The a d d i t i o n of s t e a r i c a c i d t o t h e  g r a p h i t e paste s e p a r a t e s by  increasing their  t h e anions a s c o r b a t e  and DOPAC from DA  o x i d a t i o n p o t e n t i a l s , but i t does not  f a c i l i t a t e t h e a b i l i t y of t h e e l e c t r o d e t o d i s t i n g u i s h between DA and  norepinephrine.  Although t h e r e  i s pharmacological  evidence  that  norepinephrine  r e c o r d e d by t h i s  does n o t c o n t r i b u t e  electrode  i n the nucleus  (Blaha & Lane,  1983),  sensitivity  the electrode  following  of  tissue  there  However,  increases  stearate-modified confirmation the nucleus receptive  of  tissue  that  increased  signals  striatum  the  dramatically  (Blaha, Jung,  & Phillips,  t h e mechanisms b y w h i c h e x p o s u r e t o  of  have n o t  the o x i d a t i o n  electrode  the general  signals  an  increases  observed  i n DA e f f l u x  microdialysis  probe capable of  t h e MPOA has y e t experiment  i n Experiment  in vivo microdialysis.  t o a s s e s s DA o r  therefore its  its  in of  a  I V a was a  metabolites  no a t t e m p t  metabolites  the  independent  Unfortunately,  s a m p l i n g DA o r  t o be d e s i g n e d ,  brain  produced by  remains c o n t r o v e r s i a l ,  f e m a l e and d u r i n g c o p u l a t i o n  in  been d e t e r m i n e d .  accumbens and s t r i a t u m d u r i n g t h e p r e s e n t a t i o n  attempted using  this  t o DA i s  the s e n s i t i v i t y  Because t h e n a t u r e  accumbens o r  is growing evidence  exposure t o b r a i n  preparation).  to the o x i d a t i o n  in  was made  in this  in  region.  Method Subjects  and  Surgery  The male L o n g - E v a n s r a t s purchased  from Charles River  experiments. sexually  receptive  stimulus  experiment  were  Canada and h o u s e d as i n t h e  The f e m a l e s u s e d i n t h i s  Sexual r e c e p t i v i t y previous  used i n t h i s  females  was i n d u c e d  experiment  i n Experiments  in these  previous  w e r e used as I V a and  f e m a l e s as i n  IVb.  the  experiments.  A group of  10 m a l e s was g i v e n a t  least  10 t e s t s  of  sexual  178 behavior  in the b i l e v e l  chambers p r i o r for  Experiment  The m a l e s were a n e s t h e t i z e d  (Page 5 9 ) .  pentobarbital nucleus  (60 m g / k g )  accumbens  stereotaxically  (N=5)  experience  These  had r e a c h e d t h e c r i t e r i a I  sexual  to surgery.  and m i c r o d i a l y s i s or t h e s t r i a t u m  using the atlas  for  the s t r i a t u m .  hollow  fiber  cellulose 250 um. the  of  either  2 mm ( n u c l e u s  single  end o f of  silica  the cannula. these  of  dental  acrylic  for  of  above t h e d e n t a l perfusion  Electrochemical  (1982)  (saponified  inserted inside  4 mm ( s t r i a t u m )  extended out  of  of  of  an 8 mm  the  around the  two  t h e d o u b l e end away  from  with  the s k u l l the  of  the  using cannula and  dialysate.  Analysis  Microdialysis  and s u b s e q u e n t  electrochemical  p e r f o r m e d u s i n g an a u t o m a t e d o n - l i n e  sample  analysis  injection  end  the  and s e r v e d as an i n l e t  and e x t r a c t i o n  of  The s i n g l e  The d o u b l e end o f  acrylic  through  extended  in the brain of  of  beyond  the cannula.  location  screws.  for  a semipermeable  t u b i n g was t h e n s t r i p p e d  the desired  and s k u l l  (1979)  The membrane  the cannula anchored t o the s u r f a c e  protruded outlet  into  implanted  epoxy  E p o x y was i n s e r t e d  tubing that  Excess s i l i c a  or  ends f l u s h w i t h t h e s u r f a c e  was i m p l a n t e d rest  the cannula.  the  and Watson  t u b i n g were  cannula.  accumbens)  sodium  w i t h an o u t s i d e d i a m e t e r  fused s i l i c a  steel  with  et a l .  end and t h e a s s e m b l y was g l u e d t o t h e  Y - s h a p e d 22 g s t a i n l e s s  strands  were  Paxinos  one end w i t h  Spectra Products)  Two s t r a n d s  other  (N=5)  The p r o b e s w e r e c o n s t r u c t e d  membrane c l o s e d a t  ester,  of  in  p r o b e s aimed a t  of P e l l e g r i n o  t h e n u c l e u s accumbens and t h e a t l a s  outlined  males  was  system  179 (Damsma e t solution MgCl, at  al.,  1989; Westerink  consisting  of  147 mM N a C l ,  and 1 mM NaPO (pH 7 . 3 )  a rate  100 u l  of  5 ul/min.  sample l o o p of  injected  into  injector  of  (HVA),  indole metabolite  was l o a d e d d i r e c t l y  (Valco)  and  metabolites  retention  phase l i q u i d  of  with solid acid, 1.5  ml/min.  of  detector  ( 1 5 0 x 4 . 8 mm, N u c l e o s i l 0.1 M acetic with  The male r a t s 48 h r  after  procedure that  for  to  acid  implantation  testing  the rats  used i n E x p e r i m e n t s  (5-  5C 18)  (pH 4 . 1 ,  with  a  adjusted  0 . 6 mM o c t a n o s u l f o n i c at a flow rate  was a c c o m p l i s h e d  (Bioanalytical a Ag/AgCl  Systems)  reference  on a t w o pen c h a r t  were t e s t e d  metabolites  and b )  acid  of  using  a  with a glassy electrode).  recorder  (Kipp).  Procedures  sexual  used i n E x p e r i m e n t  and i t s min;  the  0.4  detection  (+700 mV v s .  Testing  acid  reverse  Chromatograms were r e g i s t e r e d Behavioral  The  t h e s e compounds was a c h i e v e d u s i n g  Electrochemical  carbon e l e c t r o d e  a  automatically  5-hydroxyindoleacetic  EDTA, and 80 m l / 1 m e t h a n o l  LC4B a m p e r o m e t r i c  into  (1981).  sodium a c e t a t e )  0 . 0 1 mM Na  tube  and M o u l d e r  chromotography  m o b i l e phase c o n s i s t i n g  1 mM  DOPAC and h o m o v a n i l l i c  HIAA) was p e r f o r m e d as d e s c r i b e d b y W e s t e r i n k Selective  mM CaCl ,  s y s t e m e v e r y 10 m i n .  quantification and t h e  A perfusion  was pumped t h r o u g h t h e d i a l y s i s  the a n a l y t i c a l its  1986).  3 mM K C 1 , 1.3  The p e r f u s a t e the  DA,  & Tuinte,  IVa,  for  sexual  behavior  of m i c r o d i a l y s i s behavior except  were t a k e n  a)  The  identical  baseline  i n each r a t ' s  were t h e n t r a n s f e r r e d I V a and I V b  probes.  was n e a r l y  that  approximately  levels  home c a g e f o r  to the t e s t i n g  ( w h i c h was n o v e l t o  to  them)  o f DA 40  chamber for  an  180 additional  40 m i n , a f t e r  which a s e x u a l l y  placed behind the screen f o r screen  initiated  terminated previous chamber  10 m i n .  a 30-min bout  by t h e r e m o v a l o f  two e x p e r i m e n t s , for  an a d d i t i o n a l  of  the  receptive  As b e f o r e ,  copulatory female.  removal  behavior  However,  t h e males remained 80 m i n a f t e r  female  removal of  of  the  w h i c h was  unlike  in the  was  the  testing  the  female.  Histology Histological  verification  using the procedures the s l i d e s  outlined  revealed that  ending w i t h i n  the t a r g e t  microdialysis  probes  Statistical  is  all  of m i c r o d i a l y s i s i n Experiment  rats  structures.  had p r o b e  The p l a c e m e n t  shown i n F i g u r e s  of  26 and  from a standard s o l u t i o n  allowed actual  concentrations  in the d i a l y s a t e s were c a l c u l a t e d  of  tracks  27.  of  each r a t .  and c o m p a r e d t o peak  containing to  each r a t  The p e r c e n t a g e  10-min sample t h r o u g h o u t  of  Baseline values over into  for  for  for the  the  each r a t .  four  Mean  S i x s a m p l e s were s u b j e c t e d  to s t a t i s t i c a l  1) t h e  10 m i n o f  first  the  compound 10-min  testing for  each  percentages  each s a m p l e a c r o s s t h e  2)  that  determined  each  each g r o u p .  baseline;  heights  procedure  b a s e l i n e was t h e n c a l c u l a t e d  the t e s t  b a s e l i n e were c a l c u l a t e d  This  t h e s e compounds t o be  was p l a c e d  rat  t h e s e compounds  each t e s t .  as t h e mean c o n c e n t r a t i o n  samples t a k e n b e f o r e  first  of  of  DA, DOPAC, HVA, and 5 - H I A A f r o m e a c h  had been r u n t h r o u g h t h e HPLC p r i o r  of  Examination  in both.groups  were m e a s u r e d f r o m t h e c h r o m a t o g r a m s  chamber.  IVa.  Analysis  Peak h e i g h t s  obtained  p r o b e s was made  10 m i n i n  5 rats  in  analysis: the  181  182  183 testing  chamber;  3) t h e  behind the screen; s e c o n d 10 m i n o f copulation. conducted  10 m i n w i t h t h e r e c e p t i v e  4) t h e  first  copulation;  and 6)  A within-subjects  for  10 m i n o f  each compound a c r o s s  method was u s e d t o c o r r e c t  wise e r r o r  that  for  occurs w i t h a large  error  Tukey method,  the elevated  number o f  of  comparisons  was  The  experiment-  repeated  to s t a t i s t i c a l  ANOVA, p o s t - h o c  the  r e p e a t e d measures  r a t e was p_<.0083 b e c a u s e s i x  e a c h compound w e r e s u b j e c t e d  each s i g n i f i c a n t  10 m i n  5)  t h e seven samples.  Bonferroni  The c o r r e c t e d  copulation;  the t h i r d  ANOVA f o r  female  measures.  repeated  samples  analysis.  For  were made u s i n g  the  p_<.05.  Results Despite  having only  48 h t o r e c o v e r  implantation  of d i a l y s i s  probes,  interest  in the r e c e p t i v e  identical  to the  experiments. removal of  the removal  Nucleus  initiated  the t e s t . of  the  showed an  immediate  by r a t s  in the  copulation within  displayed Most r a t s  was  previous 20 s o f  normal p a t t e r n s  the  of  went t o s l e e p w i t h i n  30  female.  Accumbens  The mean p e r c e n t a g e 10-min samples apparent  displayed  t h e s c r e e n and a l l  copulation during min of  rats  10 r a t s  surgical  female behind the screen t h a t  interest  All  all  from the  is depicted  are several  Transferring  of  baseline in Figure  important  e a c h male f r o m t h e  DA r e l e a s e  for  28 ( P a n e l A ) .  changes  each of  the  Clearly  i n DA r e l e a s e .  home cage t o t h e t e s t i n g  chamber  184 i n c r e a s e d DA l e v e l s sample  an a v e r a g e o f  in the t e s t i n g  slightly  over  the next  baseline during the additional  chamber.  two s a m p l e s ,  f o u r t h sample.  10% d u r i n g t h e  increase  i n DA l e v e l s .  it  Although the removal  of  those  80-mln p e r i o d  following  DA l e v e l s  DA l e v e l s  increased  baseline)  the  levels  the removal of  the  from the baseline  the  5 rats  when t h e  s a m p l e was n o t  significantly the screen, However, another  although the  for  throughout  DA r e l e a s e  pK.OOOl.  in the t e s t i n g  chamber  c o p u l a t i o n were  t h e samples of  sample o f  increased screen,  first  (p_<.08  10-min but  not female  copulation  copulation differed  behind  was. f r o m one  significantly.  The mean p e r c e n t a g e  of  baseline  over  significantly  from the  f r o m t h e sample w i t h t h e third  the  Post-hoc  A l t h o u g h DA l e v e l s  different  and  decline  f e m a l e was p l a c e d b e h i n d t h e  two s a m p l e s o f  different  none o f  sample.  8% and  female.  t h e samples were  significantly  sample w i t h t h e males a l o n e The f i r s t  of  first  46%  in a steady  effect  all  that  female  respectively.  r e m a i n e d above b a s e l i n e  comparisons  revealed  toward  an  an a d d i t i o n a l  female r e s u l t e d  P(5,20)=16.88,  >.05).  increased  d u r i n g t h e second  t h e seven samples t e s t e d ,  this  back  The s a m p l e t a k e n d u r i n g t h e  The ANOVA d e t e c t e d a s i g n i f i c a n t  4 of  increased  10-min sample d u r i n g w h i c h t h e  96% o v e r  i n DA l e v e l s ,  in  10-min  began t o d r i f t  10-min samples t a k e n d u r i n g c o p u l a t i o n ,  increased  first  c o p u l a t i o n was a s s o c i a t e d w i t h an a d d i t i o n a l  16% ( t o a maximum o f third  the  A l t h o u g h DA l e v e l s  was p l a c e d b e h i n d t h e s c r e e n . 10 m i n o f  28% d u r i n g  DOPAC, HVA, and  5-HIAA  185 release i s depicted  i n F i g u r e 28  (Panel B).  Smaller  p a t t e r n s of r e l e a s e were observed f o r each of these compared to the p a t t e r n of DA were higher  Generally,  delayed  metabolites l e v e l s of  HVA  throughout the t e s t than l e v e l s of DOPAC, which i n  t u r n were higher metabolite  release.  and  than l e v e l s of 5-HIAA.  The  l e v e l s of each  i n c r e a s e d g r a d u a l l y when the males were t r a n s f e r r e d  from t h e i r home cage to the t e s t i n g chamber. increases i n metabolite female behind  Very s m a l l  l e v e l s accompanied the placement of  the s c r e e n .  L e v e l s of each m e t a b o l i t e  f u r t h e r d u r i n g the t h r e e samples of c o p u l a t i o n . athough the  l e v e l s of each m e t a b o l i t e  t h a t f o l l o w e d the removal of the  decreased  the  increased  As with  DA,  d u r i n g the  80  min  female, a l l remained above the  baseline. The  ANOVA d e t e c t e d  significant effects  a c r o s s the s i x  samples f o r DOPAC, F ( 5, 20 ) =16 . 58, p_<.0001; HVA, p_<.0004; and  5-HIAA, F( 5, 20) =12 . 24,  p_<.0001.  F( 5, 20 ) =8 . 68,  Post-hoc  comparisons r e v e a l e d t h a t l e v e l s of a l l m e t a b o l i t e s  were e l e v a t e d  s i g n i f i c a n t l y from b a s e l i n e d u r i n g the sample t h a t the p l a c e d behind  the s c r e e n and  c o p u l a t i o n , but not were p l a c e d  female  d u r i n g the three samples of  i n the f i r s t  10-min sample t h a t the males  i n the t e s t i n g chamber.  However, o n l y l e v e l s  DOPAC were i n c r e a s e d s i g n i f i c a n t l y d u r i n g the  first  in  the s c r e e n .  HVA  and  5-HIAA l e v e l s  of female  increased s i g n i f i c a n t l y  the t h i r d 10-min sample d u r i n g c o p u l a t i o n compared to  d u r i n g the placement of the female behind  of  10 min  c o p u l a t i o n compared to l e v e l s d u r i n g the placement of the behind  was  the  screen.  levels  186  Figure  28.  L e v e l s o f DA and i t ' s m e t a b o l i t e s i n d i a l y s a t e s f r o m t h e n u c l e u s accumbens d u r i n g p h a s e s o f s e x u a l b e h a v i o r i n E x p e r i m e n t IVc (n = 5 ) . Values are means + SE. A: C h r o m a t o g r a m d e p i c t i n g c h a n g e s i n DA l e v e l s f r o m b a s e l i n e b e f o r e , d u r i n g , and a f t e r a 3 0 min t e s t of c o p u l a t i o n . B: C h r o m a t o g r a m d e p i c t i n g c h a n g e s f r o m b a s e l i n e i n t h e l e v e l s o f DOPAC, HVA, and 5 - H I A A b e f o r e , d u r i n g , and a f t e r t h e 3 0 - m i n t e s t of c o p u l a t i o n . M i c r o d i a l y s i s and s u b s e q u e n t e l e c t r o c h e m i c a l a n a l y s i s was p e r f o r m e d u s i n g an a u t o m a t e d o n - l i n e sample i n j e c t i o n s y s t e m . D i a l y s a t e s were s a m p l e d e v e r y 10 m i n . The q u a n t i f i c a t i o n o f DA, DOPAC, HVA, and 5 - H I A A was p e r f o r m e d u s i n g r e v e r s e phase l i q u i d c h r o m a t o g r a p h y . Mean c o n c e n t r a t i o n s + SE ( f m o l / m i n ) : DA: 3 . 0 9 + 0 . 6 2 ; DOPAC: 7 7 2 . 9 5 + 1 0 2 . 9 4 ; HVA: 4 4 4 . 3 0 + 6 5 . 8 5 ; 5 - H I A A : 4 2 5 . 2 4 + 4 8 . 5 4 .  NUCLEUS ACCUMBENS 240 -i 220 -  DOPAMINE  187  188 Striatum The mean p e r c e n t a g e Figure  29 ( P a n e l A ) .  of  baseline  In general,  l e s s marked i n t h e s t r i a t u m t h a n the t e s t .  Transferring  DA r e l e a s e  the p a t t e r n  10-min sample  increase  another  appreciably while  10%.  ( t o a maximum o f  samples of  decreased  in the  however, above  chamber.  t h e males were  copulation,  the  the removal  as w i t h t h e n u c l e u s a c c u m b e n s ,  of  the  DA d i d  not  chamber.  i n c r e a s e d DA l e v e l s  respectively.  80 m i n f o l l o w i n g  during  the  in the t e s t i n g  during  these  7%, 9%, and 24% first,  second,  Levels  o f DA  of  the  levels  female, remained  baseline. The ANOVA d e t e c t e d a s i g n i f i c a n t  samples  tested,  revealed  that  significantly None o f one  accumbens  Levels  i n c r e a s e d an a d d i t i o n a l  44% above b a s e l i n e )  and t h i r d  was  i n DA r e l e a s e d u r i n g  female behind the screen  DA l e v e l s  DA r e l e a s e  each male f r o m t h e home cage t o  in the t e s t i n g  Placing a receptive  in  of  i n the nucleus  t e s t i n g chamber p r o d u c e d a 9% i n c r e a s e first  is depicted  effect  F( 5 , 20 ) =13 . 2 9 , p_<.0001 .  for  DA o v e r  Post-hoc  the other  were  i n comparison w i t h the b a s e l i n e  samples  t e s t e d was s i g n i f i c a n t l y  six  comparisons  o n l y t h e t h r e e samples d u r i n g c o p u l a t i o n increased  the  sample.  different  from  another. The mean p e r c e n t a g e  depicted increases  in Figure in the  compared t o  29  generally higher  (Panel B ) .  levels  increases  of b a s e l i n e  of  DOPAC, HVA, and 5 - H I A A  As w i t h t h e n u c l e u s  these metabolites  i n the  than levels  levels of  of  were  is  accumbens,  delayed  DA, and l e v e l s  of  DOPAC, w h i c h i n t u r n w e r e  HVA w e r e higher  189 than l e v e l s levels  of  5-HIAA.  However,  b o t h DOPAC and HVA i n c r e a s e d  c o m p a r a b l e t o DA, an e f f e c t  accumbens.  The l e v e l s  following  placment  Placement  of  the  of  of  steadily  throughout  levels.  the  test  HVA d e c r e a s e d a p p r e c i a b l y levels  of  The ANOVA d e t e c t e d for  of  Metabolite  chamber.  levels  copulation.  5-HIAA d i d significant  slight  increased  Levels  of  revealed that  in the t e s t i n g  levels  effects  across  the  HVA, b u t  Levels  of  all  from both baseline  previous  samples.  5-HIAA.  sample o f However,  Levels  c o p u l a t i o n compared t o  of  copulation for  HVA i n c r e a s e d in contrast  DOPAC and 5 - H I A A ,  samples d u r i n g c o p u l a t i o n were s i g n i f i c a n t l y another.  in  screen  significant  f e m a l e b e h i n d t h e s c r e e n was d e t e c t e d  during the t h i r d  sample of  A  10-  and t h e s a m p l e  sample w i t h t h e  HVA o r  first  f e m a l e was p l a c e d b e h i n d t h e copulation.  5-HIAA,  metabolites  the  for  the  six  n o t DOPAC o r  increase during  not  of  Post-hoc  from baseline d u r i n g the  samples of first  of  chamber.  chamber when t h e  and d u r i n g t h e t h r e e  but  DOPAC and  not.  F( 5 , 20 ) =12 . 7 9 , p_<.0001.  were i n c r e a s e d s i g n f i c a n t l y the t e s t i n g  the t e s t i n g  gradually  i n t h e 80 m i n f o l l o w i n g r e m o v a l  were i n c r e a s e d s i g n i f i c a n t l y min sample  increased  nucleus  DOPAC, F( 5 , 20 ) =17 . 4 9 , p_<.0001; HVA, F( 5, 20 ) =60 . 04 ,  p_<.0001; and 5 - H I A A , comparisons  into  in the  female behind the screen produced a  in metabolite  samples  observed  each m e t a b o l i t e  t h e males  increase  female whereas  not  to  for  the DOPAC  significantly  with the none o f  different  two the  f r o m one  190  Figure  29.  L e v e l s o f DA and i t s m e t a b o l i t e s i n d i a l y s a t e s f r o m t h e s t r i a t u m d u r i n g phases of s e x u a l b e h a v i o r i n Experiment IVc (n = 5 ) . V a l u e s a r e means + SE. A : C h r o m a t o g r a m d e p i c t i n g c h a n g e s i n DA l e v e l s f r o m b a s e l i n e b e f o r e , d u r i n g , and a f t e r a 3 0 - m i n t e s t o f copulation. B: C h r o m a t o g r a m d e p i c t i n g c h a n g e s f r o m b a s e l i n e i n t h e l e v e l s o f DOPAC, HVA, and 5 - H I A A b e f o r e , d u r i n g , and a f t e r t h e 3 0 - m i n t e s t o f copulation. M i c r o d i a l y s i s and s u b s e q u e n t e l e c t r o c h e m i c a l a n a l y s i s was p e r f o r m e d u s i n g an a u t o m a t e d o n - l i n e sample i n j e c t i o n s y s t e m . D i a l y s a t e s were s a m p l e d e v e r y 10 m i n . The q u a n t i f i c a t i o n o f DA, DOPAC, HVA, and 5 - H I A A was p e r f o r m e d u s i n g r e v e r s e phase l i q u i d c h r o m a t o g r a p h y . Mean c o n c e n t r a t i o n s + SE ( f m o l / m i n ) : DA: 5 . 9 0 + 1 . 6 2 ; DOPAC: 7 0 9 . 7 3 + 1 9 3 . 5 2 ; HVA: 6 7 0 . 3 4 + 9 9 . 8 6 ; 5 - H I A A : 4 4 7 . 3 9 + 3 1 . 0 9 .  A  STRIATUM DOPAMINE  191  240 220 200 -  U Z  180 -  Ul  iu.  160 -  o  140 -  o  s  120 100 -  SCREEN REMOVED 80 60 - •  I  IN HOME CAGE T  1 20  1  FEMALE IN  1 40  1—I—T 80 60  B  T  1  FEMALE OUT 1  100  -I 140  1—  120  1  1  1  160  1  1  1  180  200  METABOLITES 240 -  • DOPAC  220 -  • HVA  200 -  •5-HIAA  180 -  3u.  160 -  o  140 -  u K Ul  a.  120 100 -  60  |SCREEN REMOVED  IN SEX BOX  80 -  IN HOME CAGE ~i—r~ 20  I FEMALE IN  T"  —1  40  60  80  100  TIME (min)  FEMALE OUT 1  1  120  1  1—  140  —I 160  1  1—  180  —I 200  192 Discussion This  experiment  metabolites  has d e m o n s t r a t e d  increase  of  male s e x u a l b e h a v i o r  s t r i a t u m d u r i n g consummatory a s p e c t s the patterns  Biochemical  analyses  of  First,  were t r a n s f e r r e d  of  DA i n d i a l y s a t e s  the  DA l e v e l s  from t h e i r  A l t h o u g h DA l e v e l s  Finally, removal  DA l e v e l s of  the  this  during copulation. copulation,  analyses but  DA l e v e l s  r e a c h i n g a peak o f  Unlike  were t r a n s f e r r e d  of  was t h e r e a n y s i g n i f i c a n t placed behind the screen.  when  the  significant  rats  5 rats  i n c r e a s e was  not  reaching  sample. the  from baseline  levels.  from  the  i n DA l e v e l s  increased gradually  levels  only  during  44% d u r i n g t h e t h i r d striatal  when  increase  10-min  rise  this  chamber.  80 m i n f o l l o w i n g  from baseline  from t h e i r  nucleus  DA i n d i a l y s a t e s  t h e n u c l e u s accumbens,  elevated s i g n i f i c a n t l y  regions.  rose s t e a d i l y ,  female but remained e l e v a t e d  striatum revealed a small  not  4 of  A second s i g n i f i c a n t  decreased d u r i n g the  biochemical  behavior.  home c a g e s t o t h e t e s t i n g 10% i n  the  change d u r i n g  96% above b a s e l i n e d u r i n g t h e t h i r d  In contrast,  sample.  of  its  anticipatory  increased s i g n i f i c a n t l y  r o s e an a d d i t i o n a l  significant.  in these  patterns  o c c u r r e d d u r i n g c o p u l a t i o n when DA l e v e l s a peak o f  DA and  and i n  from the  f e m a l e was p l a c e d b e h i n d t h e s c r e e n ,  statistically  of  o f male s e x u a l  release d i f f e r e d  accumbens r e v e a l e d t h r e e d i s t i n c t experiment.  levels  i n t h e n u c l e u s accumbens d u r i n g  and c o n s u m m a t o r y a s p e c t s  However,  that  10-min  DA l e v e l s when t h e  were males  home c a g e t o t h e t e s t i n g  chamber,  i n c r e a s e when t h e r e c e p t i v e  female  Moreover,  striatal  DA l e v e l s  did  nor was  not  193 remain e l e v a t e d  from b a s e l i n e f o l l o w i n g the removal of the  female. These r e s u l t s p r o v i d e previous  an important  r e s u l t s u s i n g voltammetry.  c o n f i r m a t i o n of the  The dramatic  i n c r e a s e i n DA  l e v e l s d u r i n g c o p u l a t i o n i s c o n s i s t e n t with the p a t t e r n of DA o x i d a t i o n s i g n a l s observed i n the nucleus Experiment IVa.  Likewise,  accumbens d u r i n g  the l a c k of any i n c r e a s e i n s t r i a t a l  DA r e l e a s e d u r i n g the p r e s e n t a t i o n of the r e c e p t i v e female, but the s m a l l and g r a d u a l both c o n s i s t e n t with  rise  i n DA r e l e a s e d u r i n g c o p u l a t i o n , are  the p a t t e r n of DA o x i d a t i o n s i g n a l s observed  i n the s t r i a t u m d u r i n g Experiment IVa.  This general  confirmation  of the r e s u l t s of Experiment IVa suggests t h a t the use of stearate-modified  g r a p h i t e paste  account of DA e f f l u x sexual  i n the nucleus  an a c c u r a t e  accumbens and s t r i a t u m d u r i n g  behavior.  At f i r s t levels  electrodes provided  glance,  i n the nucleus  female behind  the l a c k of a s i g n i f i c a n t  i n c r e a s e i n DA  accumbens d u r i n g the p r e s e n t a t i o n of the  the s c r e e n  appears somewhat i n c o n s i s t e n t with the  r e s u l t s of the voltammetry experiments.  However, i t must be  remembered t h a t the paradigm used i n the m i c r o d i a l y s i s experiments was d i f f e r e n t . the males were g i v e n  During  the m i c r o d i a l y s i s experiments,  40 min i n the t e s t i n g chamber b e f o r e the  p r e s e n t a t i o n of the female, whereas d u r i n g the voltammetry experiments the males were p l a c e d least  i n the t e s t i n g chamber f o r a t  2 hr p r i o r t o the p r e s e n t a t i o n of the female.  This  i n c o n s i s t e n c y was unplanned but f o r t u n a t e i n t h a t i t r e v e a l e d  two  194 p o t e n t i a l l y important was  placed  increases  The  Experiment IVc may  another when the  reflect  not cleaned  elevated  In a d d i t i o n , the chamber was  DA  levels.  environment f o r the males.  have c o n t r i b u t e d  the males were alone  p o s s i b l e t h a t DA  a  i n the  last  l e v e l s would have r e t u r n e d  (Panel  It is i f the the  the  t h a t the r e l a t i v e l y extended time the males spent i n  the voltammetry experiments may  to r e t u r n to b a s e l i n e v a l u e s presentation  of the  This hypothesis  of  the.female  have p e r m i t t e d  which, i n t u r n , allowed  female to e l e v a t e DA  levels  environments and  DA the  the e f f e c t s  o l f a c t o r y cues from r e c e p t i v e  r e s u l t s of Experiment IVc extend the p r e v i o u s u t i l i z a t i o n and  levels  significantly.  r e q u i r e s f u r t h e r examination, as do  by demonstrating t h a t DA increased  28  Thus, i t seems  the t e s t i n g chamber p r i o r to the p r e s e n t a t i o n  The  the  i n the t e s t i n g chamber, as  of a female behind the s c r e e n .  and  novel  to b a s e l i n e  males i n the voltammetry experiments d i d p r i o r to  of novel  still  10-min sample  i n the t e s t i n g chamber.  spent more time alone  presentation  to  However, as shown i n F i g u r e  A), a s l i g h t downward t r e n d developed  during  in  between t e s t s i n t h i s experiment  c o p u l a t i o n s may  plausable  was  levels  f a c t t h a t these l e v e l s were  the odor of p r e v i o u s  males had  i n DA  female behind the s c r e e n the  female  f o l l o w i n g placement of the males i n the t e s t i n g chamber.  chamber was  while  when the male  lack of a f u r t h e r s i g n i f i c a n t r i s e  d u r i n g the placement of the  The  r e l e a s e : one  i n the t e s t i n g chamber and  introduced.  elevated  i n DA  females. findings  possibly synthesis  i n both the nucleus accumbens and  striatum  during  are  sexual behavior. microdialysis  Although the temporal r e s o l u t i o n of  i s not s u f f i c i e n t t o d i s t i n g u i s h the dynamic  changes i n DA e f f l u x initiation  f o l l o w i n g e j a c u l a t i o n or p r e c e d i n g the  of a c o p u l a t o r y s e r i e s , t h i s technique  compounds t o be analyzed  a t once.  In the nucleus  l e v e l s of HVA and DOPAC showed d i s t i n c t the t e s t .  In g e n e r a l ,  magnitude than l e v e l s of DA. metabolites had  was delayed  several  accumbens,  p a t t e r n s of change d u r i n g  l e v e l s of HVA were higher  DOPAC throughout t h e t e s t , although  allows  than l e v e l s of  both were s m a l l e r i n  In a d d i t i o n , the p a t t e r n of both  r e l a t i v e t o t h a t of DA.  L e v e l s of HVA  i n c r e a s e d s i g n i f i c a n t l y from b a s e l i n e when the female was  p l a c e d behind  the screen  sample of c o p u l a t i o n .  and f u r t h e r d u r i n g the t h i r d  However, although  10-min  l e v e l s of HVA  decreased  a f t e r the t e s t of c o p u l a t i o n , they d i d not r e t u r n t o b a s e l i n e . L e v e l s of DOPAC had i n c r e a s e d p l a c e d behind  the s c r e e n ,  and i n c r e a s e d f u r t h e r d u r i n g the f i r s t  10-min sample of c o p u l a t i o n . returned  from b a s e l i n e when the female was  U n l i k e HVA, l e v e l s of DOPAC  t o b a s e l i n e by the end of t h e t e s t .  accumbens, s t r i a t a l  As i n the nucleus  l e v e l s of HVA were g e n e r a l l y higher  l e v e l s of DOPAC throughout the t e s t .  than  However, l e v e l s of HVA  i n c r e a s e d s i g n i f i c a n t l y when the males were t r a n s f e r r e d t o t h e t e s t i n g chamber, f u r t h e r when the female was p l a c e d behind t h e screen,  and again d u r i n g the t h i r d  10-min sample of c o p u l a t i o n .  F o l l o w i n g t h e t e s t of c o p u l a t i o n , l e v e l s of HVA s l i g h t l y but d i d not reach  baseline levels.  decreased  DOPAC l e v e l s  i n c r e a s e d s i g n i f i c a n t l y from b a s e l i n e when the female was p l a c e d  196 b e h i n d t h e s c r e e n and f u r t h e r copulation.  However,  to baseline  following  unlike  during the HVA, l e v e l s  of  10-min sample  DOPAC d e c r e a s e d  synthesis  of  the postsynaptic  DA, r e s p e c t i v e l y .  utilization  This  is  because  (COMT; t h e enzyme t h a t  to  c o n v e r t e d s u b s e q u e n t l y t o HVA)  found  in highest  monoamine o x i d a s e  which i s  concentrations  is  found i n highest  presynaptic 1986). levels of  pools  of  increases  in levels  compelling  evidence  of  accompanied by i n c r e a s e s the nucleus  these s t r u c t u r e s (Ahlenius  et  al.,  results  the  first  and m e s o s t r i a t a l  3,4to  within  Bloom & R o t h ,  may r e f l e c t  DA s y n t h e s i s  metabolism and  and u t i l i z a t i o n .  the sexual behavior i n DA s y n t h e s i s  that  the  the nerve t e r m i n a l ,  This  thus The  the t e s t  provide  o f male r a t s  is  and u t i l i z a t i o n  in  is consistent  with  DOPA a c c u m u l a t i o n  during the copulatory behavior  increases o f male  both  in  rats  1987).  Taken t o g e t h e r , provide  fluid  accumbens and s t r i a t u m .  ex v i v o  Cooper,  is  whereas  in mitochondria  HVA and DOPAC t h r o u g h o u t  that  cleft  DA  s u b s e q u e n t l y c o n v e r t e d t o HVA b y COMT,  DA w i t h i n  may s e r v e as a measure o f  DA t o  converts  is converted subsequently  (see e . g . ,  DOPAC i n e x t r a c e l l u l a r  nonreleased  previous  which  converts  concentration  nerve t e r m i n a l s  A l t h o u g h DOPAC i s of  in the postsynaptic  ( t h e enzyme t h a t  dihydroxyphenylacetaldehyde DOPAC)  back  and  catechol-o-methyl-transferase 3-methoxytyramine  of  copulation.  HVA and DOPAC c a n r e f l e c t presynaptic  first  the r e s u l t s  direct  evidence  terminals,  of Experiments that  IVa,  DA r e l e a s e  and c a t e c h o l a m i n e  in  release  IVb,  and  IVc  mesolimbic in  197 d i e n c e p h a l i c DA t e r m i n a l s , the male r a t .  increased  Increased  DA r e l e a s e  the p r e s e n t a t i o n  i n i t i a t i o n of c o p u l a t i o n .  i n the nucleus  of a s e x u a l  accumbens  i n c e n t i v e , and the  In c o n t r a s t , DA r e l e a s e d i d not  i n the s t r i a t u m d u r i n g the p r e s e n t a t i o n  i n c e n t i v e but i n c r e a s e d  of a s e x u a l  gradually during copulation.  r e s u l t s g i v e t e n t a t i v e support  These  t o the hypotheses generated i n  Experiments II and I I I t h a t mesolimbic and d i e n c e p h a l i c systems p l a y a comparable r o l e behavior  i n a n t i c i p a t o r y aspects  DA of s e x u a l  whereas mesolimbic, m e s o s t r i a t a l , and d i e n c e p h a l i c  systems p l a y a r o l e behavior.  in  catecholamine r e l e a s e i n the MPOA were both  a s s o c i a t e d with  increase  behavior  However, these systems appear t o be a c t i v a t e d  differentially. and  increases during sexual  i n d i f f e r e n t aspects  of consummatory  DA  sexual  198 GENERAL DISCUSSION  The experiments accomplish  r e p o r t e d i n t h i s t h e s i s were undertaken  two o b j e c t i v e s .  The f i r s t  to  was t o d e s c r i b e the r o l e of  b r a i n DA systems i n a n t i c i p a t o r y and consummatory a s p e c t s of s e x u a l behavior to  i n male r a t s .  The second  was t o r e l a t e t h i s  role  the more g e n e r a l one p l a y e d by b r a i n DA systems i n the  r e g u l a t i o n of i n c e n t i v e m o t i v a t i o n . accomplished  These o b j e c t i v e s were  u s i n g an i n t e g r a t e d approach c o m p r i s i n g b e h a v i o r a l ,  p h a r m a c o l o g i c a l , and e l e c t r o c h e m i c a l t e c h n i q u e s . this  Accordingly,  f i n a l s e c t i o n begins w i t h a summary of the major f i n d i n g s . It  was n e c e s s a r y f i r s t  t o e s t a b l i s h a standard b e h a v i o r a l  framework w i t h i n which t o view the components of male s e x u a l behavior  and, with both o b j e c t i v e s i n mind, t o p r o v i d e a c l e a r  c o n c e p t u a l and b e h a v i o r a l d i s t i n c t i o n between a n t i c i p a t o r y and consummatory a s p e c t s of male s e x u a l b e h a v i o r . accomplished  i n Experiment  by Mendelson and G o r z a l k a  T h i s was  I u s i n g the b i l e v e l chambers (1987).  These chambers allowed a  measure of a n t i c i p a t o r y s e x u a l b e h a v i o r , l e v e l (Mendelson & Pfaus, 1989), to be analyzed  changing  immediately  i n t r o d u c t i o n of a s e x u a l l y r e c e p t i v e female  from a standard t e s t of s e x u a l behavior  to  b e f o r e the  and the s t a r t  20-min t e s t of consummatory c o p u l a t o r y b e h a v i o r .  were gathered  designed  of a  Normative d a t a  i n the b i l e v e l  chambers  from s e x u a l l y experienced male r a t s and s u b j e c t e d  m u l t i p l e c o r r e l a t i o n and f a c t o r a n a l y s e s i n Experiment  I.  c o r r e l a t i o n a l a n a l y s e s r e p l i c a t e d the r e s u l t s of a p r e v i o u s  The study  199 by Sachs  (1978),  copulatory  and c o n f i r m e d  behavior  were r e l a t e d  c h a n g i n g was s t a t i s t i c a l l y copulatory behavior test.  Factor  analysis  factors all  Hit  Rate,  accounted  with least  analysis  of  Copulatory  five  sexual  factors:  for  over  80% o f  of  o f male s e x u a l that  behavior,  measures of  these  level  changing,  to those  The s t a t i s t i c a l  receptor  t o assess t r e a t m e n t s revealed several  antagonists  sexual behavior. neuroleptics antagonist  on a n t i c i p a t o r y  Systemic  haloperidol  that  chambers,  and  anticipatory  of  sexual  consummatory  t o use  affect  of  behavior  measures of  striking  at  theoretical  between these c l a s s e s  changing i n c o n j u n c t i o n w i t h t r a d i t i o n a l  II  that  separation  rationale  for  associated  i n any  as a measure o f  and p r o v i d e d an i m p o r t a n t  Experiment  These  indicated  independent  axes  variance  factor  results  and c o n s u m m a t o r y m e a s u r e s o f  behavior  the  the  f o u n d by Sachs  in the b i l e v e l  was s t a t i s t i c a l l y  supported the general d i s t i n c t i o n  sexual  of  Rate,  intersubject  an A n t i c i p a t i o n  behavior  sexual behavior.  anticipatory  behavior,  the  identical  Together,  of  and A n t i c i p a t i o n .  c o n c e p t u a l mechanisms w e r e r e q u i r e d  established  level  t h e n i n e measures  rotation  Mount C o u n t ,  changing.  five  of  of  However,  using orthogonal  with the a d d i t i o n  level  measures  statistically.  independent  m e a s u r e s and w e r e n e a r l y  (1978),  several  a n a l y z e d d u r i n g t h e consummatory phase o f  revealed the existence Initiation,  that  further  of  level consummatory  DA t r a n s m i s s i o n .  effects  o f DA  and c o n s u m m a t o r y m e a s u r e s  administration  and p i m o z i d e ,  of  the  and t h e  typical  Dl-selective  SCH 2 3 3 9 0 , d o s e - d e p e n d e n t l y d e c r e a s e d t h e number  of  of  200 level  changes,  increased the  d e c r e a s e d t h e number o f ejaculations. selective  t h e number o f  every case,  the  anticipatory  sexual  of  or  DA a n t a g o n i s t s  behavior.  number o f  behavior  measures of  haloperidol,  pimozide,  c h a n g i n g and t h e results  differentially sexually active demonstrated  sexual  previous  but d i d In  level  almost  to  significantly  that  affect  to the  other  behavior.  of  copulatory  findings  (Pfaus  that  disruptive  in  and to  such  reflected  initiation  or  consistent  reports  synergistic  of  these r e s u l t s of  copulation. actions  indicated  D l o r D2 r e c e p t o r s  of  In a d d i t i o n ,  D I - and D 2 - s e l e c t i v e  t h a t ithe r e l a t i v e l y  had s i m i l a r  effects  level  antagonists  behavior  c h a n g i n g was more s e n s i t i v e  or  These  DA r e c e p t o r  1989),  the  of  t h a n were consummatory measures t h a t of  of  reduced  doses  behavior.  & Phillips,  of  consummatory  Higher  copulatory  of  t h e measure  disruption  rate  not  changing  agent metoclopramide  measures o f  male r a t s  that  level  or c l o z a p i n e d e l a y e d or a b o l i s h e d  disrupt  D2-  t h a n were consummatory measures  initiation  replicated  level  was more s e n s i t i v e  but d i d not  anticipatory  and t h e  of  o r d e c r e a s e t h e number  indicating  The a n t i e m e t i c  intromissions  number  ejaculations.  to decrease  latencies  ejaculations,  sexual  or  latencies,  than those required  intromission  intromissions  effects  intromissions  were l o w e r  clozapine  and  r e d u c e d t h e number o f  intromission  t h e doses r e q u i r e d  significantly increase  the  latencies,  and t h e t o t a l  neuroleptic  sulpiride  c h a n g e s and i n c r e a s e d affect  intromissions  The a t y p i c a l  antagonist  intromission  selective  the with  compounds, antagonism  on a n t i c i p a t o r y  and  201 consummatory measures Experiment affects  III  provided the  anticipatory  behavior  DA t e r m i n a l s ,  these regions  aspects  first  in different  MPOA, w e r e c h o s e n f o r that  mesolimbic affecting  are  involved  initiation  Bilateral  major  terminal  of  total  number o f  copulation  infusions  other  but did not  or consummatory s e x u a l  infusions  haloperidol  of of  without  consummatory  behavior.  increased  other  terminal  of  produced n e a r l y a l l  effects  administration,  including  of  level  changes,  increased  d e c r e a s e d number o f results are  intromissions  suggested t h a t  involved  copulatory  in the d i s p l a y copulation,  of  respectively, anticipatory  copulatory  Finally,  two  of  latencies,  rate,  in vivo  of  number  These striatum  sexual behavior  w h e r e a s DA i n t h e MPOA i s sexual behavior,  and h i t  the  and a  and e j a c u l a t i o n s .  anticipatory  the  a decreased  DA i n t h e n u c l e u s accumbens and  in the display  rate,  intromission  of  Unilateral  A14 DA p a t h w a y ,  systemic  a  the  measures  incertohypothalamic of  the  to the s t r i a t u m ,  affect  t o t h e MPOA, a m a j o r  and  consummatory  terminal  A9 DA p a t h w a y ,  anticipatory of  or  of  changing  of h a l o p e r i d o l  the m e s o s t r i a t a l  ejaculations  level  Three  evidence  infusions  a major  attenuated  of  of previous  Bilateral  sexual  striatum,  in the c o n t r o l  t o t h e n u c l e u s accumbens,  the  haloperidol  regions.  accumbens,  s t u d y on t h e b a s i s  A10 DA p a t h w a y ,  measures.  evidence t h a t  DA t e r m i n a l  the nucleus  of male s e x u a l b e h a v i o r .  haloperidol  behavior.  and c o n s u m m a t o r y m e a s u r e s o f male  selectively  forebrain  o f male s e x u a l  the  and  involved  initiation  of  rate.  electrochemical  techniques,  voltammetry  202 and  m i c r o d i a l y s i s , were used  i n Experiment IV t o examine DA  efflux  i n t h e nucleus accumbens and s t r i a t u m ,  efflux  i n the MPOA, d u r i n g  of s e x u a l  behavior  and c a t e c h o l a m i n e  a n t i c i p a t o r y and consummatory phases  i n s e x u a l l y a c t i v e male r a t s .  A unilevel  t e s t i n g chamber was used i n these experiments because t h e particular construction  of t h e b i l e v e l chambers p r e c l u d e d t h e  f r e e movement of r a t s with voltammetry or m i c r o d i a l y s i s assemblies p r o t r u d i n g  from t h e i r heads.  However, a new p r o t o c o l  was used i n these experiments t h a t comprised an a n t i c i p a t o r y phase, i n which t h e males were p l a c e d access t o a s e x u a l l y r e c e p t i v e and  female behind a s c r e e n  f o r 5 min,  a consummatory phase, i n which removal of t h e s c r e e n  the animals t o engage i n c o p u l a t o r y In t h e f i r s t revealed and  i n t o t h e chamber and g i v e n  behavior.  of these experiments, chronoamperometry  t h a t DA e f f l u x i n the nucleus accumbens and s t r i a t u m ,  catecholamine e f f l u x i n t h e MPOA, i n c r e a s e d  during  allowed  the two phases of s e x u a l  behavior.  accumbens, DA o x i d a t i o n s i g n a l s i n c r e a s e d female was p l a c e d  behind the s c r e e n ,  differentially  In t h e nucleus when the r e c e p t i v e  and i n c r e a s e d  most r a t s p r i o r t o t h e i n i t i a t i o n of c o p u l a t i o n . s i g n a l s were maintained throughout t h e f i r s t  further i n These  copulatory  increased series.  E j a c u l a t i o n was accompanied by an immediate decrease i n DA o x i d a t i o n s i g n a l s ; however, these s i g n a l s remained e l e v a t e d baseline an  levels.  increase  Each r e i n i t i a t i o n  from  of c o p u l a t i o n was preceded by  i n the DA o x i d a t i o n s i g n a l s .  In c o n t r a s t , the DA  o x i d a t i o n s i g n a l s i n t h e s t r i a t u m were not a f f e c t e d  significantly  by the placement of a r e c e p t i v e female behind the s c r e e n . However, those s i g n a l s i n c r e a s e d  g r a d u a l l y throughout t h e  consummatory phase but d i d not correspond t o any p a r t i c u l a r aspect  of c o p u l a t o r y  behavior.  i n the MPOA r e v e a l e d  Catecholamine o x i d a t i o n s i g n a l s  a s m a l l e r , but n e a r l y i d e n t i c a l p a t t e r n t o  t h a t observed f o r DA o x i d a t i o n s i g n a l s i n the nucleus accumbens. These r e s u l t s  indicated that  increased  accumbens and catecholamine e f f l u x with  the p r e s e n t a t i o n  DA e f f l u x  i n the MPOA were a s s o c i a t e d  of a n a t u r a l s e x u a l  i n c e n t i v e and with the  i n i t i a t i o n of c o p u l a t i o n , whereas DA e f f l u x increased The  n o n s p e c i f i c a l l y during  second experiment of t h i s s e r i e s examined t h e by a n a l y z i n g  oxidation  i n t h e nucleus accumbens, s t r i a t u m , and MPOA d u r i n g t h e  presentation  of e i t h e r a male, a n o n r e c e p t i v e  smeared with  estrous  behind the s c r e e n . significantly  Oxidation  Oxidation  female  s l i g h t l y but  t h e p r e s e n t a t i o n of  female, or the s l i d e , but i n c r e a s e d  the presentation  of the r e c e p t i v e  female.  s i g n a l s i n the MPOA i n c r e a s e d s i g n i f i c a n t l y d u r i n g the  presentation  of both t h e s l i d e and r e c e p t i v e female, but not  the p r e s e n t a t i o n  of t h e s t i m u l i striatum.  s i g n a l s increased  i n the nucleus accumbens d u r i n g  dramatically during  female, a s l i d e  v a g i n a l s e c r e t i o n s , or a r e c e p t i v e  the male, the n o n r e c e p t i v e  during  i n the s t r i a t u m  copulation.  s p e c i f i c i t y of the e l i c i t i n g s t i m u l u s signals  i n the nucleus  increased  of the male or n o n r e c e p t i v e  female.  oxidation signals s i g n i f i c a n t l y  None  i n the  These r e s u l t s suggested t h a t the i n c r e a s e s i n  o x i d a t i o n s i g n a l s observed i n the nucleus accumbens and MPOA  204 during the p r e s e n t a t i o n experiment  a receptive  may have been s p e c i f i c  incentive. increases  of  However,  signals  the p r e s e n t a t i o n  of  to the  DA i n t h i s  idea t h a t  processing of In the used t o  final  of  of  this  DA and i t s  sexual  levels  trend  toward a f u r t h e r  presentation further  of  baseline  levels.  metabolite smaller  gradual  utilization release  increase  lend  during support  role  increase  in the  during  in  the  nucleus  Biochemical  i n DA r e l e a s e  when odors,  in dialysates  during copulation,  the placement  synthesis,  and a and  decreased  not decrease analysis  of  back  synthesis,  b u t no s i g n i f i c a n t  of  the  d e c r e a s e d back t o b a s e l i n e  of  to  a  and increase  i n DA  t h e t h e male i n  female behind the  in the  in  DA and  from the s t r i a t u m revealed  i n DA r e l e a s e ,  80 m i n  a  the  A l t h o u g h DA l e v e l s  biochemical  analysis  nucleus  increase during  they did  was  anticipatory  from the  or m e t a b o l i s m d u r i n g t h e p l a c e m e n t  DA l e v e l s  female  metabolites  i n DA r e l e a s e ,  copulation,  increase  chamber o r d u r i n g  accumbens  female behind the s c r e e n ,  In contrast,  levels  sexual  microdialysis  behavior.  significant  during copulation.  80 m i n f o l l o w i n g  a  significant  a chamber c o n t a i n i n g c o p u l a t o r y  the receptive  significant  utilization the  into  of  a general  series,  in dialysates  accumbens r e v e a l e d a s i g n i f i c a n t males were p l a c e d  plays  10-min i n t e r v a l s  and c o n s u m m a t o r y p h a s e s o f DA and m e t a b o l i t e  but  i n the nucleus  structure  experiment  examine l e v e l s  previous  cues.  accumbens and s t r i a t u m a t  of  smaller  t h e m a l e and n o n r e c e p t i v e  incentive  in the  to the presentation  the r e l a t i v e l y  i n DA o x i d a t i o n  female  the  screen.  following  205 copulation. increases  These r e s u l t s  i n DA e f f l u x  in the nucleus  observed w i t h voltammetry those r e s u l t s  during sexual  the r o l e  behavior  motivation.  of  first  experiment  increases  accompany t h e  have i m p o r t a n t  is clear  the  and  extended  utilization  i n DA r e l e a s e  implications  regulation  are discussed  B r a i n DA Systems from the present  that  behavior  more s e n s i t i v e  However,  certain  of  of  that  male incentive  Behavior  brain  DA s y s t e m s  o f male r a t s  that  measure o f  sexual  b e i n g a n a l y z e d as on t h e p a r t i c u l a r  investigation.  models  below.  i n Male S e x u a l results  in the sexual  for  in the c o n t r o l  t o d e p e n d as much on t h e p a r t i c u l a r  behavior  of  striatum  i n DA  increases  b r a i n DA s y s t e m s  These i m p l i c a t i o n s  p l a y a complex r o l e appears  accumbens and  and i n t h e more g e n e r a l  The R o l e o f It  confirmation  behavior.  These f i n d i n g s  sexual  in the  by d e m o n s t r a t i n g t h a t  and p o s s i b l y s y n t h e s i s  consider  provided a general  DA s y s t e m u n d e r  aspects  of  sexual  behavior  to the general d i s r u p t i o n  of  b r a i n DA s y s t e m s  are than  others. Anticipatory One o f  Sexual t h e most  Behavior important  pronounced s e n s i t i v i t y changing,  to disruption  Haloperidol, significantly  pimozide,  of  in Experiment  the a n t i c i p a t o r y  by t y p i c a l clozapine,  decreased r a t e s  not s i g n i f i c a n t l y  findings  increase the  of  measure,  and a t y p i c a l  was  level  sulpiride  c h a n g i n g a t doses t h a t  latency to  the  DA a n t a g o n i s t s .  SCH 2 3 3 9 0 , and level  II  initiate  level  did  changing  206 and t h a t ,  with  few e x c e p t i o n s ,  measures of  sexual  hal.operidol  to  behavior  striatum did not.  1985),  et  al.,  of  role  suggest  of  that  or  that  level  copulatory  behavior  1 9 8 6 ; Hansen e t 1974),  of  evidence  copulate.  This  two i n v i v o  least  al.,  II  DA s y s t e m s of  that  inference  when a male r a t  techniques,  in the  DA a g o n i s t s  & Stinus, a of  of  the  sexual operate.  can  al.,  1973; T a g l i a m o n t e  et  al.,  DA a c t i v i t y  anticipates  the  i n Experiment  and  when a s e x u a l l y r e c e p t i v e of  increases  opportunity IV  to  using  microdialysis.  DA and c a t e c h o l a m i n e  initiation  stimulate et  was t h a t  voltammetry  provided  (Dallo  n u c l e u s accumbens and MPOA, r e s p e c t i v e l y ,  s c r e e n and d u r i n g t h e  1987;  nucleus  anticipatory  was c o n f i r m e d  Voltammetry revealed t h a t  i n male r a t s  al.,  aspects  and I I I  how t h o s e s y s t e m s  1982; Malmnas,  inference  the  t w o f o r e b r a i n DA  i n s e x u a l l y s l u g g i s h males  t h e most o b v i o u s  in those regions  at  III  to  DA s y s t e m s p l a y  preparatory  of Experiments  they d i d not s p e c i f y of  1974; K e l l e y  of  changing.  a necessary r o l e  in l i g h t  infusions  Blackburn et  central  accumbens and MPOA i n t h e c o n t r o l  However,  infusions  accumbens and MPOA, f o r m p a r t  Although the r e s u l t s  behavior,  (e.g.,  et a l . ,  in anticipatory  the nucleus  of  feeding  and i n d i c a t e  neural c i r c u i t r y  evidence  Central  c h a n g i n g whereas  1977; F i b i g e r  sexual behavior, terminals,  level  As w i t h  these r e s u l t s  preferential  significantly.  consummatory  t h e n u c l e u s accumbens and MPOA i n E x p e r i m e n t  also decreased r a t e s  Blundell  did not a f f e c t  increases  efflux  in  the  dramatically  f e m a l e was p l a c e d b e h i n d  copulation.  Similarly,  a  207  m i c r o d i a l y s i s confirmed a s i g n i f i c a n t  increase  i n DA  release in  the nucleus accumbens when the male was  t r a n s f e r r e d to a chamber  containing copulatory  toward a s i g n i f i c a n t  increase during increase  i n DA  odors and  a trend  the p r e s e n t a t i o n levels  of a r e c e p t i v e female.  i n the nucleus accumbens t h a t  The  accompanied  the placement of the males i n the t e s t i n g chamber i s i n t e r e s t i n g i n l i g h t of the  f i n d i n g t h a t h a l o p e r i d o l decreased r a t e s of  level  changing f o l l o w i n g i n f u s i o n t o the nucleus accumbens i n Experiment I I I .  In both cases,  chamber t h a t c o n t a i n e d To  the extent  odors from p r e v i o u s  Consistent increase  in a testing  t e s t s of  copulation.  t h a t these c o n d i t i o n s are comparable, i t would seem  l i k e l y t h a t a dynamic i n c r e a s e changing and  males were p l a c e d  perhaps other  with  i n DA  i n DA  release potentiates  forms of a n t i c i p a t o r y s e x u a l  level behavior.  the r e s u l t s of Experiment I I I , t h e r e was efflux  i n the s t r i a t u m d u r i n g  no  the p r e s e n t a t i o n  the r e c e p t i v e female, thus i t would seem t h a t m e s o s t r i a t a l systems are not behavior.  MPOA d i s p l a y e d a d i f f e r e n t  i n the  nucleus  p a t t e r n of  increase  the placement of e i t h e r a male, a n o n r e c e p t i v e  s l i d e smeared with  estrous  female behind the s c r e e n .  female, a  v a g i n a l s e c r e t i o n s , or a r e c e p t i v e A l l of these s t i m u l i  oxidation signals s i g n i f i c a n t l y  increased  increase  the  i n the nucleus accumbens,  although placement of the r e c e p t i v e female induced s i g n i f i c a n t l y greater  DA  i n the c o n t r o l of a n t i c i p a t o r y s e x u a l  Interestingly, oxidation currents  accumbens and during  involved  of  a  i n the o x i d a t i o n s i g n a l s .  c o n t r a s t , o n l y the placement of s l i d e or the e c e p t i v e  In  female  208 increased  the o x i d a t i o n s i g n a l s s i g n i f i c a n t l y  i n the MPOA.  Moreover, t h e magnitude of t h e o x i d a t i o n s i g n a l s d u r i n g t h e placement of t h e r e c e p t i v e  female was not s i g n i f i c a n t l y  from those observed d u r i n g  the during  t h e placement of t h e s l i d e .  Although these data i n d i c a t e t h a t t h e i n c r e a s e s i g n a l s observed i n both of these r e g i o n s to t h e p r e s e n t a t i o n  of a s e x u a l  different  i n oxidation  isrelatively  specific  i n c e n t i v e , they suggest t h a t the  nucleus accumbens and MPOA p r o c e s s cues from a r e c e p t i v e  female  differently. Differences  between mesolimbic and d i e n c e p h a l i c  the c o n t r o l of a n t i c i p a t o r y a s p e c t s of male s e x u a l not new.  E v e r i t t e t a l . (1987) r e p o r t e d  l e s i o n s of t h e MPOA had no e f f e c t  that  nuclei i n  behavior a r e  ibotenic acid  on r a t e s of bar p r e s s i n g by  male r a t s f o r a secondary s e x u a l  incentive  associated  of a s e x u a l l y r e c e p t i v e  with the p r e s e n t a t i o n  In c o n t r a s t , E v e r i t t  (a s t i m u l u s  light female).  e t a l . (1989) showed t h a t b i l a t e r a l N-  methyl-D-aspartate l e s i o n s of the b a s o l a t e r a l amygdala, a structure that contains  DA r e c e p t o r s  major mesolimbic DA t e r m i n a l ,  and t h a t l i e s c l o s e t o a  the c o r t i c o m e d i a l  d r a m a t i c a l l y reduced r a t e s of bar p r e s s i n g sexual  incentive.  amygdala,  f o r t h e secondary  I n t e r e s t i n g l y , t h e b a s o l a t e r a l amygdala sends  a f f e r e n t p r o j e c t i o n s t o t h e nucleus accumbens and i n f u s i o n s of damphetamine t o the nucleus accumbens of r a t s with those l e s i o n s restored  r a t e s of bar p r e s s i n g .  Assuming t h a t Everitt  l e s i o n s o f the MPOA i n t h e e a r l i e r  et a l . (1987) reduced DA input  study by  from the zona i n c e r t a , a  209 treatment t h a t should antagonist,  have been s i m i l a r t o i n f u s i o n s of a DA  i t must be concluded t h a t the MPOA, and i t s DA  i n n e r v a t i o n , does not c o n t r i b u t e i n bar p r e s s i n g first  glance,  t o the n e u r a l  f o r a secondary s e x u a l  circuitry  incentive.  involved  Although a t  those r e s u l t s appear i n c o n s i s t e n t with t h e  e f f e c t i v e n e s s of h a l o p e r i d o l  i n f u s i o n s t o t h e MPOA i n r e d u c i n g  r a t e s of l e v e l changing, t h e r e  a r e important d i f f e r e n c e s between  the types of s t i m u l i responded t o by r a t s i n t h e two paradigms. The  chambers used i n t h e present  between t e s t s of s e x u a l  experiments were not c l e a n e d  b e h a v i o r , thus i t i s c o n c e i v a b l e  odor of p r e v i o u s  copulations  may c o n t r i b u t e  l e v e l changing.  Those odors may p r o v i d e  that the  t o the d i s p l a y of  unconditioned  olfactory  cues and may have d i r e c t and r e l a t i v e l y s e l e c t i v e access t o hormone s e n s i t i v e MPOA neurons.  The MPOA r e c e i v e s a l a r g e  e f f e r e n t p r o j e c t i o n from the c o r t i c o m e d i a l terminalis  (Krettek  & P r i c e , 1978).  The c o r t i c o m e d i a l  in turn, receives efferent projections organ and t h e o l f a c t o r y bulbs  amygdala v i a the s t r i a amygdala,  from both the vomeronasal  (Lehman & Winans, 1982).  It is  i n t e r e s t i n g t o note t h a t o l f a c t o r y s t i m u l i from a female r a t evoke e l e c t r i c a l a c t i v i t y c a s t r a t e d male r a t s  will  i n t h e MPOA. of i n t a c t , but not  ( P f a f f & Pfaffmann, 1969).  In c o n t r a s t , i t  i s u n l i k e l y t h a t odor cues c o n t r i b u t e t o t h e r a t e s of barp r e s s i n g assessed by E v e r i t t present  i n t h e chamber.  e t a l . , as such cues were not  Although l i t t l e  f u n c t i o n of t h e i n c e r t o h y p o t h a l a m i c  i s known about t h e  DA neurons t h a t p r o j e c t t o  the MPOA, t h e c e l l bodies w i t h i n t h e zona i n c e r t a t h a t g i v e  rise  210 to  this  projection  intrinsic of not  hypothalamic  Experiment  III,  contribute  MPOA.  receive diffuse  it  neurons  to the processing of  may be i n v o l v e d  in the expression  Consummatory S e x u a l level  DA a n t a g o n i s t s ,  moderate doses of of  copulatory of  copulatory  rate  count  (e.g.,  treatment  latencies  these neurons information  Everitt  or  (1987;  1989)  DA i n t h e MPOA forms  of  accumbens and  behavior.  d i d not  (e.g.,  it  the  by s m a l l  affect  altogether.  doses  sulpiride  increased  intromission  by and  the  and  antagonist  latencies  o r mount c o u n t .  d e c r e a s e d t h e number o f  and mount  intromission  intromissions  C l o z a p i n e and t h e D 2 - s e l e c t i v e  copulatory rate  latency),  pimozide,  SCH 23390 i n c r e a s e d t h e  and d e c r e a s e d t h e number o f  aspects  were a f f e c t e d  Haloperidol,  by  The  ejaculations),  intromissions)  the  other  intromission  t h e number o f  antagonist  than  c o n s u m m a t o r y m e a s u r e s were a f f e c t e d  eliminate  t h e number o f  metoclopramide  the  both olfactory-dependent  sexual  these drugs t h a t  (e.g.,  measures o f  that  did  by  olfactory-dependent  ejaculations.  affect  et a l .  copulation to disruption  several  copulation  both  results  c h a n g i n g was g e n e r a l l y more s e n s i t i v e  w i t h DA a n t a g o n i s t s .  Dl-selective  Given the  Behavior  behavior  initiation  of  other  w h e r e a s DA i n t h e n u c l e u s  anticipatory  consummatory measures o f of  if  suggest  i n the expression of  forms of  Although  of  from  1987).  sensory  experiments  sexual behavior  may b y i n v o l v e d intependent  the r e s u l t s  the present  anticipatory  (Moore,  w o u l d be s u r p r i s i n g  Taken t o g e t h e r ,  and t h o s e o f  innervation  intromissions  but d i d In  not  contrast,  but d i d  not  211 affect  the  doses of  initiation  of  haloperidol,  pimozide,  decreased the p r o p o r t i o n Central affect  infusions  of  copulation  of  or c o p u l a t o r y  and c l o z a p i n e  rats  haloperidol  consummatory measures o f  that  Higher  signficantly  initiated  copulation.  to the nucleus sexual  rate.  accumbens d i d  behavior.  Infusions  not  of  t  haloperidol systemic  t o t h e MPOA p r o d u c e d n e a r l y a l l  administration,  latencies  and a d e c r e a s e d number o f  ejaculations. striatum  Surprisingly,  increased,  ejaculations. results  rather  Unlike  indicate  in certain rat,  including  that  elements  including  intromissions,  the  of  example,  decrease  of  facilitation  and to  t h e number  of  literature,  the  these  of  intromissions,  male  t h e number  to reconcile  DA a n t a g o n i s t s  some o f  in the  in the  of  ejaculations.  is d i f f i c u l t of  behavior  role  the  effects  intromission  ejaculations  on  these  consummatory  are  paradoxical.  l a t e n c y or  a  c a n be i n t e r p r e t e d  as a  consummatory s e x u a l m o t i v a t i o n whereas a d e c r e a s e of  intromissions  (e.g.,  delays  erections  c a n be i n t e r p r e t e d  Sachs & B a r f i e l d ,  experiments  haloperidol penile  Indeed,  an i n c r e a s e  i n t h e number  of  effect  i n t h e number o f  disruption  series  it  intromission  haloperidol  feeding  consummatory s e x u a l  initiation  with a simple  of  of  DA s y s t e m s p l a y an i m p o r t a n t  and t h e number o f  sexual m o t i v a t i o n . For  from the  effects  intromissions  infusions  central  As n o t e d p r e v i o u s l y , results  increased  than decreased,  data  the  by Pehek e t a l .  seminal  1976).  However,  (1988a)  demonstrated  e m i s s i o n and d e c r e a s e s  d i s p l a y e d by i n t a c t ,  as a a  critical that  t h e number  sexually active  male  of  rats.  212 These f i n d i n g s  offer  the  haloperidol  effects  of  decreased a b i l i t y  of  a parsimonious  explanation  on c o n s u m m a t o r y s e x u a l b e h a v i o r .  a rat  t o g a i n or m a i n t a i n  treatment  with haloperidol  latencies  and d e c r e a s e t h e number o f  seminal  test  of  copulatory  In circumstances it  or w i t h o u t  intromission,  latencies,  as an i n d e x  haloperidol Experiment play a role penile  of  Thus,  in the  it  following  the  delayed  during  a  are d i s r u p t e d  t o use mount to the  drug  latencies  with  intromission  to  initiate  copulation.  SCH 2 3 3 9 0 , and  i n Experiment  II.  sulpiride Infusions  i n c r e a s e d t h e mount l a t e n c i e s  may be c o n c l u d e d t h a t  initiation  by  of  brain  of  in  DA s y s t e m s  c o p u l a t i o n and i n t h e c o n t r o l  of  reflexes.  DA f u n c t i o n  haloperidol  sexual behavior,  infusions  of  it  activity  i n t h e MPOA f a c i l i t a t e s Such a r o l e  been s u g g e s t e d p r e v i o u s l y apomorphine t o e i t h e r  for  initiation  diencephalic  on t h e b a s i s  and MPOA  III.  Because  t h e same e f f e c t  c o u l d be i n f e r r e d the  inferences  striatum,  Experiment  t o t h e MPOA had n e a r l y  administrations,  erection.  several  i n t h e n u c l e u s accumbens,  systemic  of  reflexes  clozapine,  c o u l d be made b a s e d on t h e r e s u l t s  penile  The  intromission  ejaculations  the m o t i v a t i o n  t o t h e MPOA a l s o III.  the  of  behavior.  t h e mount l a t e n c i e s  As w i t h a n t i c i p a t o r y about  fewer  in addition  haloperidol,  erection  intromissions;  may be more a p p r o p r i a t e  Interestingly, increased  increase  where p e n i l e  treatments  all  should  emission should lead to  standard  to nearly a l l  that of  i n c r e a s e d DA copulation  DA s y s t e m s  of,evidence  as  that  t h e MPOA o r p a r a v e n t r i c u l a r  and  has  infusions  nucleus  213 facilitate  both the  (Pehek e t a l . , increase to the  1988b).  was a s s o c i a t e d  an i n h i b i t i o n  of  evidence  continue despite  that  the  fact  investigate  with  an i n t e r e s t  that  Larsson, release  MPOA may t h u s The l a c k on c o p u l a t i o n this  structure  of  regions  sexual behavior. t h e DA a g o n i s t following  to  of  III  to  the  penile with  of  failed  the nucleus  but  will and  without  1 9 8 2 ; Heimer & suggest  that  erection lesions  DA  and  of  the  erection. accumbens  DA a c t i v i t y  with previous  accumbens  there  females  consummatory measures  to affect  was  t h e MPOA  females  in the nucleus  suggested t h a t  Each  However,  Such m a l e s  to gain penile  for  be  interval  lesions  thrusting  in rats  T h i s was c o n s i s t e n t  infusions  in part,  i n t h e MPOA.  these r e s u l t s  haloperidol  required  apomorphine  of  facilitate  a failure  i n Experiment was n o t  may,  1984; Hansen,  copulation  effect  the  in sexually receptive  & Edwards,  of  reflect  sexual  electrolytic  Taken t o g e t h e r ,  The l a c k  of  the p o s t e j a c u l a t o r y  the anogenital  i n t h e MPOA s e r v e s  mounting.  oxidation  t h e y do n o t c o p u l a t e .  (Brackett  1966).  in the  efflux  o c c a s i o n a l l y d i s p l a y mounts w i t h p e l v i c intromission  Ejaculation  in the oxidation s i g n a l s .  male r a t s  to display  after  IV.  ejaculation  catecholamine  an  i n t h e MPOA p r i o r  in Experiment  part  erections  suggestion,  was o b s e r v e d  following  of c o p u l a t i o n  and p e n i l e  with this  w i t h an i m m e d i a t e d e c r e a s e  p r e c e d e d b y an i n c r e a s e  often  efflux  copulation  o f male r a t s  reinitiation  is  copulation  i n t h e MPOA, s u g g e s t i n g t h a t  quiescence due t o  of  of  Consistent  in catecholamine  initiation  signals  initiation  of  reports  copulatory (Hull  in  et  that  behavior al.,  1986).  214 However,  Everitt  et a l .  (1989)  amphetamine t o t h e n u c l e u s intromission that  latencies  of  the  voltammetry efflux  of  to catecholamine DA e f f l u x  copulatory  series  DA f u n c t i o n DA r e l e a s e  in this  haloperidol sufficient results  efflux  is  the nucleus  following  several  et  that  III  i n c r e a s e mount o r  al.  (1989) of  accumbens d u r i n g c o p u l a t i o n increased a c t i v i t y  activation  of  for  activation  However, behavior,  of  DA t e r m i n a l s  given the general it  seems u n l i k e l y  the  would tend t o DA e f f l u x  in the nucleus  that  First,  of  The support  observed  i n t h e MPOA.  in  IV could Because  forebrain it  of  about  not  i n Experiment  of  each  initiation  latencies.  to a c t i v a t i o n  importance  in of  dose  was  1 9 7 6 ; Swanson, 1 9 7 6 ) ,  t h e MPOA l e a d s  DA  possibilities  i n t h e MPOA s e n d a x o n s t h r o u g h t h e m e d i a l  t o t h e VTA ( C o n r a d & P f a f f ,  of  was  larger  the highest  intromission  both  ejaculation.  (10 u g / s i d e )  Second, t h e p a t t e r n  an e p i p h e n o m e n o n o f  that  initiation  each  may be n e c e s s a r y  conceivable  r e p o r t e d by E v e r i t t  IV,  a dynamic p a t t e r n  the  and  could  In Experiment  to  d-  suggesting  accumbens d u r i n g c o p u l a t i o n .  used i n E x p e r i m e n t to  of  rats,  i n t h e MPOA b u t  data suggest  structure  It  hypothesis.  hence,  revealed  and d e c r e a s e d  in the nucleus  copulation.  that  copulation.  increased p r i o r  The e l e c t r o c h e m i c a l  bodies  Lister  i n t h e n u c l e u s accumbens  and m i c r o d i a l y s i s  magnitude.  this  sexually active  initiation  infusions  i n t h e n u c l e u s accumbens d u r i n g c o p u l a t i o n  identical  of  that  accumbens d e c r e a s e d t h e mount  i n c r e a s e d DA a c t i v i t y  facilitate  reported  is  be  cell  bundle  possible  t h e VTA a n d ,  accumbens.  the nucleus  accumbens  t h e dynamic changes o b s e r v e d  in in  215 Experiment MPOA.  It  I V were r e s i d u a l m i g h t be u s e f u l  precopulatory  for  the  that  1976)  is  into  DA r e l e a s e  expression of  the  initiation  programs  for  nucleus  accumbens c o u l d be s u f f i c i e n t ,  higher  a " g a t i n g " mechanism.  copulation.  doses of  receptor  haloperidol,  antagonists,  or  is  sexual  or  "gated" To  necessary  behavior, and t h u s  way,  DA r e l e a s e  in  not  necessary,  for  of  infusion  p e r h a p s more s e l e c t i v e  need t o be e x a m i n e d  the  copulation.  effects  in the  accumbens d u r i n g c o p u l a t i o n b e f o r e a n y o f be  of  but  the  1956)  copulation  In t h i s  Clearly,  of  of  that  accumbens  aspects  of  of  (Beach,  in the nucleus  motor  activation  an h y p o t h e s i s  as p a r t  initiation  similar  "summed"  anticipatory  may s e r v e t o s e n s i t i z e  of  to consider  sexual arousal  (Sachs & B a r f i e l d , the extent  effects  it act  the the  of  DA  nucleus  these p o s s i b i l i t i e s  can  rejected. The r o l e  behavior  of  striatal  is d i f f i c u l t  infusions  to  i n c r e a s e d DA a c t i v i t y ejaculation.  envisioned possible,  establish.  As n o t e d a b o v e ,  to the s t r i a t u m i n Experiment  than decreased the t o t a l  unclear.  DA i n c o n s u m m a t o r y a s p e c t s  ejaculations,  The mechanisms  of  effect  such i n h i b i t i o n , on p e n i l e  the antagonism of  although haloperidol  to  d i d not  ejaculation  however,  are  as c a n be  t h e number  intromissions  or t h e  microdialysis  both revealed t h a t  progressively  in the s t r i a t u m during c o p u l a t i o n but,  DA e f f l u x  that  inhibit  i n t h e MPOA,  affect  latency.  rather  suggesting  reflexes,  DA a c t i v i t y  sexual  haloperidol  increased,  i n the s t r i a t u m serves  An i n h i b i t o r y for  number o f  III  of  Voltammetry  is of  and  increases unlike  216 efflux  in the nucleus  any p a r t i c u l a r  accumbens o r MPOA, i s  aspect  of  copulation.  not associated  The i n c r e a s e d r e l e a s e  i n t h e s t r i a t u m d u r i n g c o p u l a t i o n c o u l d be an a r t i f a c t motor  activity.  Ahlenius  c o p u l a t i o n and 25 m i n o f increases light  of  the e f f e c t  of  lesions 1989),  III,  it  tempting  nervous  infusions  (Brackett  et  al.,  that  incompatible  1988)  an e j a c u l a t o r y  that  inhibition  different  and s e n s i t i z a t i o n  b r a i n a r e a s and t h a t  supersede those of  inhibition.  examine t h e e f f e c t  striatal  selective  DA a n t a g o n i s t s  1967),  it  (e.g.,  Clearly,  infusions  in greater  of  it  the  simultaneously  or  in  eventually  be n e c e s s a r y  haloperidol  detail.  Sachs  sensitize  that  processes will  Bitran &  1976;  is conceivable  sensitization  the  originally  serve to  could occur  of  this  idea  by o t h e r s  in  inhibition  1 9 8 1 ; Sachs & B a r f i e l d ,  However,  al.,  that  Although  w i t h the  m o u n t i n g and i n t r o m i t t i n g  mechanism.  et  components  (Konorski,  and r e i t e r a t e d  1988; Crowley & Zemlan,  & Meisel,  mutual  (1956)  and  i n c r e a s e d DA a c t i v i t y  thrusting,  in  6-OHDA  be e x p e c t e d t o e s t a b l i s h m u t u a l  s u g g e s t i o n seems somewhat  In  initiation or  of  significant  1986; Robbins  e j a c u l a t o r y mechanisms.  processes  Hull,  in  c e r t a i n motor  between such i n c o m p a t i b l e  p r o p o s e d b y Beach  general  the s t r i a t u m  electrolytic  s u c h as m o u n t i n g o r p e l v i c  system might  to  o f DA  b o t h 10 m i n  led to  with the d i s r u p t i o n s  to suggest  temporarily antagonize  of  i n t h e s t r i a t u m of male r a t s .  the s t r i a t u m serves to regulate copulation,  noted t h a t  locomotion  i n d u c e d by e i t h e r  the s t r i a t u m is  (1987)  haloperidol  together  copulation of  of  al.  treadmill  i n DOPA s y n t h e s i s  Experiment rate  et  with  more  to  217 B r a i n DA Systems and Male Sexual The may  A Synthesis  f o r e g o i n g d i s c u s s i o n i l l u s t r a t e s how b r a i n DA systems  c o n t r o l a n t i c i p a t o r y and consummatory a s p e c t s of male s e x u a l  behavior  at d i f f e r e n t  l e v e l s of n e u r a l p r o c e s s i n g .  as a n a t u r a l cascade of events, to  Behavior:  ejaculation,  What appears  from a n t i c i p a t i o n t o i n i t i a t i o n  i s dependent on the s u c c e s s f u l s w i t c h i n g of motor  programs as t h e topography of the s e x u a l i n c e n t i v e changes from attractivity  to p r o c e p t i v i t y to r e c e p t i v i t y .  Two b r a i n areas i n  which DA appears t o modulate male s e x u a l b e h a v i o r , the MPOA and nucleus  accumbens, f i g u r e p r o m i n e n t l y  system f o r the e x e c u t i o n of motivated proposed by Mogenson, Jones, subsequently  by Toates  Briefly, an animal's the animal  behavior  originally  and Yim (1980) and m o d i f i e d  (1986) and Sachs and M e i s e l  (1988).  f o r e b r a i n s t r u c t u r e s s e r v e as an i n t e r f a c e between  m o t i v a t i o n a l s t a t e and the motor systems t h a t a l l o w t o a c t on e x t e r n a l i n c e n t i v e cues.  a f f e r e n t s from a v a r i e t y of s o u r c e s , b u l b s , amygdala, and hypothalamus. thus  i n the n e u r a l l y - b a s e d model  The MPOA r e c e i v e s  i n c l u d i n g the o l f a c t o r y The MPOA and i t s e f f e r e n t s  form a common pathway f o r the i n t e g r a t i o n of an animal's  hormonal s t a t e , the presence environmental  of an e s t r o u s female, the  c o n t e x t , and p r e v i o u s e x p e r i e n c e .  i s t r a n s m i t t e d v i a the medial  This information  f o r e b r a i n bundle t o the d o r s a l and  v e n t r a l tegmentum, where i t i s r e l a y e d i n p a r t t o t h e nucleus accumbens.  The nucleus  accumbens a l s o r e c e i v e s i n p u t s from  s e v e r a l other s o u r c e s , most n o t a b l y the amygdala.  By v i r t u e of  i t s d i f f u s e connections, with the b a s a l g a n g l i a , the nucleus  218 accumbens i s viewed as an i n t e r f a c e between m o t i v a t i o n and action. The sexual  present  r e s u l t s suggest t h a t the p r e s e n t a t i o n  of a  i n c e n t i v e , such as the odor or presence of an e s t r o u s  female behind a s c r e e n ,  i n c r e a s e s DA r e l e a s e and metabolism i n  d i e n c e p h a l i c and mesolimbic DA t e r m i n a l s .  This  increased  s e n s i t i z e s both t h e MPOA and t h e nucleus accumbens the hypothalamus t o f a c i l i t a t e  release  simultaneously  and  stimulates  and  t h e b a s a l g a n g l i a t o f a c i l i t a t e t h e motor programs n e c e s s a r y  for  the d i s p l a y of a n t i c i p a t o r y s e x u a l  D i s r u p t i o n of DA a c t i v i t y  penile erections  behaviors  and mounting.  i n the MPOA or nucleus accumbens  p r o g r e s s i v e l y d e c r e a s e s the l i k e l i h o o d  of a complete  transition  from s e x u a l  motivation  t o a n t i c i p a t o r y or consummatory forms of  male s e x u a l  behavior.  The present  with T o a t e s '  (1986) model of sexual  r e s u l t s a r e a l s o compatible motivation,  which  recognizes  a complex i n t e r a c t i o n between e x t e r n a l  i n c e n t i v e s t i m u l i and  i n t e r n a l hormonal s t a t e i n d e t e r m i n i n g  sexual  s e n s i t i z a t i o n of an e j a c u l a t i o n mechanism. levels elicited  a r o u s a l and t h e  The i n c r e a s e  i n DA  by cues from a r e c e p t i v e female may be an  e s s e n t i a l neural substrate  f o r processes  of s e x u a l  arousal.  Toates a l s o p o s t u l a t e s t h a t e j a c u l a t i o n , i n t u r n , l e a d s t o the d e s e n s i t i z a t i o n of s e x u a l  arousal.  The c l e a r and d r a m a t i c drop  i n both t h e DA o x i d a t i o n s i g n a l i n the nucleus accumbens and t h e catecholamine o x i d a t i o n s i g n a l i n the MPOA f o l l o w i n g e j a c u l a t i o n i s e n t i r e l y c o n s i s t e n t with  this postulation.  However, i t must be remembered t h a t DA t e r m i n a l s  exist  elsewhere  in the b r a i n .  No s t u d i e s  have y e t  DA t e r m i n a l s  i n the  amygdala,  or  olfactory  bulbs.  behavior  of  other  male s e x u a l b e h a v i o r c.orticomedial i n male s e x u a l as t h o s e of  of  i n t h e median eminence,  of  DA f u n c t i o n  educated  is  important i n terms  and t h e c l i n i c a l systems.  DA t e r m i n a l s ,  such  is  Finally,  unknown.  1987;  of  role  i n more d e t a i l .  filled,  the  remain l i t t l e  Kaplan,  into  treatments  four  (e.g.,  there  sexual  of  that  Introduction,  1974; Masters  sexual d e s i r e , in,  of  i n the  c a n be d i v i d e d  the r e s u l t s  the organization  impact  As n o t e d  two p h a s e s ,  engage  the  Until  description  more  than  Implications  to consider  o r g a s m , and r e s o l u t i o n  of  diencephalic  p r e s e n t e d above w i l l  Similarly,  speculation.  experiments  cycle  cortex, role  i n knowledge are  Clinical It  frontal  in  the  DA i n the* s t r i a t u m needs t o be e x a m i n e d  s u c h t i m e as t h e s e gaps  determined a r o l e  phases,  of  the  human s e x u a l affect  t h e human s e x u a l appetitive,  1966).  activity;  subjective  and p h y s i o l o g i c a l  excitement  before  of  fantasies  and s e x u a l a r o u s a l , changes t h a t  and d u r i n g c o p u l a t o r y  Psychiatric  Association,  reminiscent  of  1987).  consummatory a s p e c t s  of  behavior  the  processes  consisting  activity  first  or a d e s i r e  accompany  This c l i n i c a l  the general d i s t i n c t i o n  Association,  between  about,  response  excitement,  Within  i s good r e a s o n t o d i s t i n g u i s h consisting  behavior  b r a i n DA  American P s y c h i a t r i c  & Johnson,  present  to  of  the  sexual  (American  distinction  between a n t i c i p a t o r y  used i n t h e p r e s e n t  is and  experiments.  220 To the extent t h a t such homologies a r e v a l i d , o f f e r some hypotheses about t h e e f f e c t antagonists  on the s e x u a l behavior  the present  results  of DA a g o n i s t s and  of human males.  T y p i c a l and a t y p i c a l DA a n t a g o n i s t s a r e used i n p s y c h i a t r i c medicine as major t r a n q u i l i z e r s and a n t i p s y c h o t i c agents. They have a l s o been used r a t h e r i n n a p r o p r i a t e l y as s e d a t i v e s and a n t i a n x i e t y drugs.  C e r t a i n DA a n t a g o n i s t s  t h a t lack  a n t i p s y c h o t i c e f f i c a c y , e.g., metoclopramide, are a l s o used as a n t i e m e t i c agents.  Among the l e s s e r  " s i d e e f f e c t s " of many of  these drugs a r e d i s o r d e r s of s e x u a l behavior i n h i b i t e d s e x u a l d e s i r e , delayed  that include  or i n h i b i t e d s e x u a l a r o u s a l , and  delayed  orgasm ( K o t i n e t a l . , 1977; P e t r i e ,  1988).  The r e s u l t s of Experiment II a r e g e n e r a l l y c o n s i s t e n t  with these c l i n i c a l  impressions.  s e x u a l d e s i r e i s extremely  I t would be p r e d i c t e d t h a t  s e n s i t i v e to d i s r u p t i o n by DA  a n t a g o n i s t s , f o l l o w e d by s e x u a l a r o u s a l . i n v o l v e an e f f e c t  of DA a n t a g o n i s t s  r e g u l a t i o n of p e n i l e e r e c t i o n .  should  The l a t t e r  on the  Difficulties  a l s o stem from the i n a b i l i t y t o achieve C l i n i c i a n s attempting  1985; Segraves,  of these  may  neuroendocrine a c h i e v i n g orgasm can  or m a i n t a i n e r e c t i o n .  t o t r e a t s e x u a l d i s o r d e r s or d y s f u n c t i o n s  be concerned about the widespread use of these drugs, and  they should  attempt t o r u l e out a " p h y s i o l o g i c a l " e t i o l o g y t h a t  stems from c o n c u r r e n t  treatment  with DA a n t a g o n i s t s .  In  a d d i t i o n , the impact of s e x u a l d i s o r d e r s or d y s f u n c t i o n s t h a t a r e induced  by treatment  therapeutic efficacy.  with DA a n t a g o n i s t s should Obviously  be assessed on  the a b i l i t y t o manage one s e t of  221 symptoms must be w e i g h e d a g a i n s t symptoms, one o f this  e s p e c i a l l y when t h e o t h e r  t h e most  end,  utilize  it  important  is  antagonists  been r e p o r t e d or  involves  pleasure  This  evidence  useful  & Davis,  1 9 8 5 ; Waud, 1 9 3 3 ) . interpretation  DA a g o n i s t s  been c o u n t e r a c t e d lisuride,  that  of  1 9 8 5 ; Bowers & Van W o e r t ,  in the treatment  of  erectile  are by  treatment  sexual  and  arousal  Parkinson's  failure,  has  t h e DA r e c e p t o r (Bartke  1972; P i e r i n i  1985).  have  example,  s u c h as  or b r o m o c r i p t i n e  et a l . ,  in the  on t h e  1-DOPA o r  DA  Hollister,  For  and r e n a l  has  or  DA a g o n i s t s  sexual desire  diabetes,  apomorphine,  1976;  are e f f e c t i v e  DA a n t a g o n i s t s  loss  cocaine,  has been s t r e n g t h e n e d  w i t h t h e DA p r e c u r s o r  1981; Ruilope  DA  Such r e p o r t s  associated w i t h c e r t a i n medical c o n d i t i o n s , hyperprolactinemia,  of  lines  stimulate  1959; C a r t e r  the  that  of drugs t h a t  of  effective  and  that  users  with the e f f e c t s  is  experiments  or a r o u s a l  s u c h as d - a m p h e t a m i n e ,  human m a l e s ,  To  sexual desire  consistent  Nusimovich,  of  human m a l e s .  and d y s f u n c t i o n s .  1983; B a r w i n ,  a disruption  of  interpretation  that  of  sexual disorders  agonists  of  procedures,  of c e r t a i n  disease,  set  along the t h e o r e t i c a l l y  by r e c r e a t i o n a l  generated a long-standing  of  another  and i n t i m a c y .  well-controlled  the s t i m u l a t i o n  Schneiden & Rees,  behavior  of  be c o n d u c t e d t o e x a m i n e t h e e f f e c t s  (Burroughs,  aphrodisiacs.  set  drug a d m i n i s t r a t i o n  receptors,  apomorphine  induction  of  on t h e s e x u a l b e h a v i o r  Conversely,  clinical  that  sexual behavior  mentioned above,  1975;  sources  imperative  double-blind  fractionate  pathways  the  Similarly, dysfunction  et  al.,  & apomorphine (e.g.,  Lai  222 et a l . , 1987).  The DA r e c e p t o r  undergoing c l i n i c a l d e s i r e and a r o u s a l  trials  agonist  as a g e n e r a l  disorders  quinpirole  i s also  treatment f o r s e x u a l  (M. Foreman,  personal  communication). The  e f f e c t i v e n e s s of DA a g o n i s t s  d e s i r e or a r o u s a l to s e x u a l  i n stimulating  suggests t h a t d i s r u p t e d  d e s i r e and a r o u s a l  disorders.  sexual  DA a c t i v i t y  contributes  Based on t h e r e s u l t s of  Experiment IV, such d i s r u p t i o n may occur i n mesolimbic or diencephalic  DA t e r m i n a l s .  However, although t h e r e i s  c o r r e s p o n d i n g evidence t h a t DA a g o n i s t s sexually delay  stimulate  copulation i n  i n a c t i v e or s l u g g i s h male r a t s , these drugs can a l s o  the i n i t i a t i o n of c o p u l a t i o n  intromissions  and reduce the number of  in sexually active rats.  these drugs as a treatment f o r s e x u a l  Thus, the u t i l i t y of d e s i r e or a r o u s a l  may be l i m i t e d t o i n d i v i d u a l s p o s s e s s i n g I t has been argued t h a t the sexual  h y p o a c t i v e DA systems. behavior of male r a t s  does not c o n s t i t u t e a v a l i d model of the s e x u a l  behavior of human  males because r a t s lack the " c o g n i t i v e c o n t r o l " t h a t to mediate human sexual  behavior  •that r a t s a r e r e a d i l y a b l e conditioning  (e.g.,  disorders  i s assumed  Wilson, 1977).  The f a c t  t o respond v i a c l a s s i c a l and operant  f o r primary and secondary s e x u a l  incentives  (Everitt  et a l . , 1987; Mendelson & P f a u s , 1989; Zamble, M i t c h e l l , & Findlay,  1986), and capable of i n h i b i t i n g t h e i r s e x u a l  with s e x u a l l y n o n r e c e p t i v e females i n d i c a t e s that higher-order responding of male r a t s .  responses  (Pfaus & P i n e l , 1989),  l e a r n i n g accompanies the sexual Moreover, many drug e f f e c t s on the  223 sexual  behavior  behavior  of  of  challenge  advantage of  to generate  treatment  Wilson's  behavior.  the r i c h  of  Clinical  literature  testable  The s e c o n d o b j e c t i v e DA i n male s e x u a l  incentive  demonstrating  that  sexual behavior  It  is clear  evidence  hoarding  al.,  (Fibiger  other  (Blundell  responses et  for  et  al.,  a CS+ t h a t  1974),  signals  role  shock  of  role DA i n  first of  by male  in extracellular  and DA  cues. behaviors  to disruption  experiments  anticipatory  the d e l i v e r y  instrumental  and c o n d i t i o n e d (Blackburn,  a r e more  sensitive  b y DA a n t a g o n i s t s .  1977), conditioned  signals  and  b y b r a i n DA s y s t e m s  increases  in the present  1987), conditioned al.,  that  forms of  t o a CS+ t h a t  et  differently  male  the  and c o n s u m m a t o r y a s p e c t s  anticipatory  T h i s was shown r e p e a t e d l y  of  Behavior  was t o r e l a t e  t o t h e more g e n e r a l  by i n c e n t i v e  that  effects  i n human m a l e s .  Motivated  thesis  the  the e t i o l o g y  T h i s was a c c o m p l i s h e d t w o w a y s ,  t h a n consummatory b e h a v i o r s  demonstrated  concerning  II.  take  on t h e s e x u a l b e h a v i o r  this  are r e g u l a t e d  are e l i c i t e d  can t h u s  and d y s f u n c t i o n s  anticipatory  second by p r o v i d i n g release  of  behavior  motivation.  researchers  as a Form o f  sexual  and u n d e r s c o r e  i n the study of drug  hypotheses  sexual disorders  on t h e  amply i n Experiment  contention  approach  Male S e x u a l B e h a v i o r  of  resemble drug e f f e c t s  as d e m o n s t r a t e d  the comparative  on male s e x u a l  rats  male r a t s  human m a l e s ,  These r e s u l t s utility  of  responding,  been  s u c h as  preparatory of  a meal  responses  for  preparatory  1989).  and has  (Blackburn food  responses  Likewise,  the  to  224 presence of  an e s t r o u s  particularly  salient  catecholamine similar that  (Blackburn et  e v o k i n g an i n c r e a s e  of  the presentation  al.,  part  suggest  DA i n t h e n u c l e u s  of  1989; P h i l l i p s ,  of  i n DA and  i n t h e n u c l e u s accumbens and MPOA.  these r e s u l t s  an i m p o r t a n t  for  increased release  accompanies  Together,  stimulus  release  to the  f e m a l e b e h i n d t h e s c r e e n was a  This  accumbens  a p r e p a r a t o r y CS+ f o r  Pfaus,  that  & Blaha,  increased  the m o t i v a t i o n a l  state  is  food  1990).  DA a c t i v i t y  induced by  forms  incentive  cues. The g e n e r a l i t y that  male s e x u a l  of  these  behavior  and o t h e r  s h a r e common n e u r o a n a t o m i c a l processing of there  are  incentive  important  forms of m o t i v a t e d experiments  is  findings  cues.  However,  behavior. of  forms of  The most o b v i o u s  b r a i n DA s y s t e m s  of  behavior.  As i n d i c a t e d  aspects  of  f e e d i n g or  a v o i d i n g do n o t  not  affected  initiation  by t r e a t m e n t  mesotelencephalic of  doses of  DA a n t a g o n i s t s  deficits. release the  above,  Moreover,  initiation  of  to  of  In contrast,  d i d not  dynamic changes  in the nucleus  and  other  present  consummatory  involve  b r a i n DA  those behaviors or  lesions  both the  by t r e a t m e n t  i n DA and  are  of  initiation  with  produce g e n e r a l  and e j a c u l a t i o n ;  the  similarities,  moderate  motor  catecholamine  accumbens and MPOA were o b s e r v e d  copulation  for  consummatory  certain  appear  and d i s p l a y  c o p u l a t i o n were a f f e c t e d that  the  in the  in  w i t h DA a n t a g o n i s t s  DA p a t h w a y s .  and r a t e  networks  despite  idea  behavior  between s e x u a l b e h a v i o r  aspects  systems because t h e  to the  motivated  and n e u r o c h e m i c a l  differences  the r o l e  lends support  during  a progressive  rise  225 in s t r i a t a l  DA r e l e a s e  Another  important  and f e e d i n g o r Blackburn  occurred  processing of  difference  avoiding  (1989)  involves  has a r g u e d t h a t  internal  delivered.  the r o l e  of  However,  in his  s t u d y were c a p a b l e  facilitate  sexual a r o u s a b i l i t y  and p e n i l e  activating  DA t e r m i n a l s  t h e MPOA o r  previous role  section,  In conclusion, infer  a general  affected  role  aspects  of  certain  behavior, behavior  the  hormonal  a neurotransmitter  feeding,  may by  in  the important  cues.  motivational  behavior,  lesions  of  it  is  Although  incorrect  to think  in  control of  behavior.  t h e MPOA d i s r u p t  maternal  in addition  1980; V a l e n s t e i n  behavior  s y s t e m s may be  in the  role  to  Comparable  prominently  and t h e r m o r e g u l a t i o n , al.,  system.  or d r u g t r e a t m e n t s .  as h a v i n g a s i n g l e  (Mogenson e t  in motivated  a single motivational  by l e s i o n s  of  although  androgens  in part  DA s y s t e m s may p l a y an  internal  of d i f f e r e n t  aspects  of  aspects  paraventricular  interpretation  p a t h w a y s may f i g u r e  neurotransmitters Similarly,  of  of  differently  neurotransmitter  with  was  Androgens  reflexes  rats  c a u t i o n must be e x e r c i s e d when a t t e m p t i n g  b a s e d on t h e s t u d y o f behavioral  most n o t a b l y t h e MPOA.  diencephalic  in the processing  once i t  on t h e b i n d i n g  brain areas,  consistent  the  of  and c o n s u m m a t o r y  to certain  Thus,  in  cues because w e l l - t r a i n e d  are dependent  within  cues.  DA does n o t p l a y a r o l e  both a n t i c i p a t o r y  behavior  behavior  internal  t h e s h o c k and e s c a p i n g s u c c e s s f u l l y  of male s e x u a l  nucleus.  copulation.  b e t w e e n male s e x u a l  or p r o x i m a l  t r e a t e d w i t h DA a n t a g o n i s t s perceiving  throughout  et  al.,  to  sexual  1970),  the  226  r o l e of d i e n c e p h a l i c DA systems i n the c o n t r o l of processes  t h a t u n d e r l i e the d i s p l a y of p e n i l e r e f l e x e s , and hence  c e r t a i n aspects  of c o p u l a t o r y b e h a v i o r ,  sexual behavior. neurotransmitter motivated  neuroendocrine  Obviously  may be s p e c i f i c t o male  i t i s unwise t o base a t h e o r y of  f u n c t i o n i n m o t i v a t i o n on a s i n g l e aspect of  behavior  d e r i v e d from a s i n g l e m o t i v a t i o n a l system.  However, should comparative a n a l y s e s  r e v e a l a common thread among  d i f f e r e n t m o t i v a t i o n a l systems, as i s becoming apparent f o r t h e g e n e r a l r o l e of mesolimbic DA pathways i n a n t i c i p a t o r y a s p e c t s of behavior,  then the g o a l of g e n e r a t i n g  t h e o r y about n e u r o t r a n s m i t t e r s  coherent  i n behavior  will  and comprehensive begin  to be  realized.  Summary and C o n c l u s i o n s The  s e x u a l behavior  of male r a t s depends upon the a c t i v i t y  of a v a r i e t y of c e n t r a l and p e r i p h e r a l n e u r a l systems t h a t i n t e g r a t e the animal's  i n t e r n a l m o t i v a t i o n a l s t a t e with the  e x t e r n a l environment.  The r o l e of both d i e n c e p h a l i c and  mesotelencephalic  DA systems i n t h i s regard can be viewed as an  i n t e r f a c e between m o t i v a t i o n and a c t i o n . these systems i n response t o a s e x u a l necessary  Increased  DA r e l e a s e i n  i n c e n t i v e may c o n s t i t u t e a  n e u r a l component of a n t i c i p a t o r y s e x u a l d e s i r e and  a r o u s a l t h a t s e n s i t i z e s p e n i l e r e f l e x mechanisms i n the hypothalamus and motor programs f o r c o p u l a t i o n i n t h e b a s a l ganglia.  T h i s i s c o n s i s t e n t with the g e n e r a l t h e o r y t h a t b r a i n  DA systems form an important  component of i n c e n t i v e m o t i v a t i o n .  227 There i s s t i l l  much to be done.  t e r m i n a l s i n male s e x u a l behavior do  i n other  forms of motivated  The  r o l e of other b r a i n  needs to be addressed,  behavior.  The  impact  drugs or n e u r o t r a n s m i t t e r s on d i e n c e p h a l i c and DA systems i n male s e x u a l behavior  as  DA  they  of other  mesotelencephalic  a l s o needs to be  assessed.  Moreover, b e f o r e a g e n e r a l r o l e can be a s s i g n e d to b r a i n DA systems i n s e x u a l b e h a v i o r , the r o l e of these systems i n female sexual behavior The  needs to be s t u d i e d i n d e t a i l .  experiments r e p o r t e d i n t h i s t h e s i s combined b e h a v i o r a l ,  pharmacological, the r o l e of DA  and  e l e c t r o c h e m i c a l techniques  i n male s e x u a l b e h a v i o r .  provided a s y s t e m a t i c way l e v e l s of a n a l y s i s .  to examine DA  T h i s combined  of  approach  f u n c t i o n at s e v e r a l  H o p e f u l l y , t h i s approach w i l l prove u s e f u l  i n f u t u r e experiments with s e x u a l behavior of motivated  i n the study  behavior.  or with other c l a s s e s  228 REFERENCES Agmo, A. & F e r n a n d e z , H. ( 1 9 8 9 ) . Dopamine and s e x u a l b e h a v i o r t h e male r a t : A r e e v a l u a t i o n . 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