UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Flight behaviour elicited by electrical stimulation of the hypothalamus and midbrain in rats : Escape… Clarke, Robert John 1972

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1972_A6_7 C43.pdf [ 3.26MB ]
Metadata
JSON: 831-1.0101727.json
JSON-LD: 831-1.0101727-ld.json
RDF/XML (Pretty): 831-1.0101727-rdf.xml
RDF/JSON: 831-1.0101727-rdf.json
Turtle: 831-1.0101727-turtle.txt
N-Triples: 831-1.0101727-rdf-ntriples.txt
Original Record: 831-1.0101727-source.json
Full Text
831-1.0101727-fulltext.txt
Citation
831-1.0101727.ris

Full Text

FLIGHT BEHAVIOUR ELICITED BY ELECTRICAL STIMULATION OF THE HYPOTHALAMUS AND MIDBRAIN IN RATS: ESCAPE AND AVOIDANCE PROPERTIES  by ROBERT JOHN CLARKE B.Sc., U n i v e r s i t y o f B r i t i s h C o l u m b i a , 1969  A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE  i n the Kinsmen L a b o r a t o r y o f N e u r o l o g i c a l  Research  DEPARTMENT OF PSYCHIATRY  We a c c e p t t h i s t h e s i s as c o n f o r m i n g t o the required  standard  THE UNIVERSITY OF BRITISH COLUMBIA May, 1972  In presenting  t h i s t h e s i s i n p a r t i a l f u l f i l m e n t of the requirements f o r  an advanced degree at the U n i v e r s i t y of B r i t i s h Columbia, I agree that the Library s h a l l make i t f r e e l y a v a i l a b l e f o r reference and study. I f u r t h e r agree that permission f o r extensive copying of t h i s thesis f o r s c h o l a r l y purposes may by h i s representatives.  be granted by the Head of my Department or I t i s understood that copying or p u b l i c a t i o n  of t h i s t h e s i s f o r f i n a n c i a l gain s h a l l not be allowed without my w r i t t e n permission.  Department of The U n i v e r s i t y of B r i t i s h Columbia Vancouver 8 , Canada  ABSTRACT Emotional, motivational, or s p e c i e s - s p e c i f i c behaviour can be e l i c i t e d by i n t r a c r a n i a l e l e c t r i c a l stimulation (ICS) i n unanesthetized and unrestrained animals with c h r o n i c a l l y implanted electrodes. The purpose of this investigation was to describe and quantify, using an escape and avoidance task, a behaviour c a l l e d f l i g h t , using rats as the experimental animal.  An enclosed test box was used that had a  hole i n one wall covered by a moveable clear p l a s t i c plate.  With the  i n t e r i o r l i g h t on and exterior l i g h t s o f f , the hole represented the only opening i n the box. F l i g h t was then operationally defined as plate-pushing i n response to ICS (escape response).  I t was found that  only 25% of rats which showed manifestations of f l i g h t on pre-test screening would perform the escape response.  After e s t a b l i s h i n g r e l i a b l e  escape, the rats were given the opportunity to avoid ICS, at the threshold voltage for escape, by responding to a s i g n a l ( b e l l , l i g h t or c l i c k ) predicting the occurrence of ICS. In over 200 t r i a l s there were at most only 107 avoidances and no tendency for faster responding. o  A current  explanation f o r t h i s , proposed by W. W. Roberts, was tested by allowing these rats to press a bar f o r b r i e f ICS at the voltage used i n avoidance. Only 407o of the subjects would self-stimulate.  These, and other r e s u l t s  from the l i t e r a t u r e suggest that rewarding onset of ICS, as i n the Roberts hypothesis, i s i n s u f f i c i e n t to explain the lack of avoidance. The electrode s i t e s producing escape were found to be i n the central gray of the midbrain, and i n both the medial and l a t e r a l d i v i s i o n s of the middle to posterior hypothalamus near the f o r n i x .  The s i t e s pro-  ducing similar behavioural manifestations but not escape were found to be i n the same regions of the hypothalamus and midbrain.  iii  TABLE OF CONTENTS Page Abstract Table  ii-  o f Contents  i i i  L i s t o f Tables  iv  L i s t of Figures  »  Acknowledgement  v vi  Introduction D e f i n i t i o n of theories (a) Emotion (b) M o t i v a t i o n  1 1 5  R e s e a r c h l e a d i n g to the p r e s e n t i n v e s t i g a t i o n (a) D e s c r i p t i o n : e f f e c t s and l o c a t i o n (b) Q u a n t i f i c a t i o n o f ICS b e h a v i o u r (c) C o n d i t i o n i n g (d) Summary  9 9 14 17 21  Methods Subjects  o  22  Surgery  .'  22  Apparatus  23  Procedure (a) S c r e e n i n g (b) Escape t r a i n i n g (c) A v o i d a n c e t r a i n i n g (d) S e l f - s t i m u l a t i o n (e) H i s t o l o g y  28 28 28 29 30 30  ;  Results Stimulation effects  32  Escape  35  Avoidance  40  Self-stimulation  44  Histology  44  Discussion  49  References  59  iv  LIST OF  TABLES  Table  I  II  Page  Type and f r e q u e n c y of s t i m u l a t i o n e f f e c t s i n hypothalamus and m i d b r a i n  34  Behaviour, l o c a t i o n , threshold t r i a l s f o r escape s u b j e c t s  36  and  number o f  I I I Mean r e s p o n s e time per s e s s i o n (+ standard f o r each s u b j e c t and WS m o d a l i t y IV  Average bar the v o l t a g e  p r e s s i n g r a t e w i t h and indicated  deviation)  w i t h o u t ICS  42 at 45  LIST OF FIGURES  Figure  Page  1  Side view of one wall of the plate box  25  2  Semischematic diagram of the escape t r a i n i n g apparatus  26  Semischematic diagram of the avoidance training apparatus  27  Mean escape time versus stimulating voltage for subjects 43, 48, 50 and 56  38  Escape latency as a function of time f o r subjects 48 and 56  39  Mean latency (+ standard deviation) per session for a l l subjects as a function of the number of t r a i n i n g sessions  41  Location of electrodes producing plate-pushing  46  3 4  5 6  7 8  escape by  Location of electrodes f a i l i n g to produce • escape by plate-pushing  47  ACKNOWLEDGEMENT  I would l i k e to thank Dr. Juhn A. Wada for his advice and encouragement i n a l l aspects of the research and preparation of this thesis.  Greatly appreciated was the technical assistance of Ed Jung  Anne Hamm and Marina Koskinen. Thanks also go to the f a c u l t y , s t a f f and students of the Kinsmen Laboratory of Neurological Research for many favours, great and small, throughout my a s s o c i a t i o n with them. The f i n a n c i a l support of the Department of Psychiatry, and the Medical Research Council of Canada through a grant to Dr. J. A. Wada i s g r a t e f u l l y acknowledged.  1  INTRODUCTION A new u n d e r s t a n d i n g motivated  b e h a v i o u r has been b r o u g h t about t h r o u g h the use o f e l e c t r o d e s  c h r o n i c a l l y implanted animals.  of the n e u r a l mechanisms o f e m o t i o n a l and  i n the b r a i n s o f u n a n e s t h e t i z e d  and u n r e s t r a i n e d  I t was found t h a t e l e c t r i c a l s t i m u l a t i o n of d i s c r e t e b r a i n  a r e a s ( i n t r a c r a n i a l s t i m u l a t i o n , ICS) c o u l d induce complex b e h a v i o u r s resembling  those seen d u r i n g normal e m o t i o n a l  and m o t i v a t i o n a l s t a t e s .  T h i s l e a d t o the development o f a method t o q u a n t i f y t h i s b e h a v i o u r and  to determine i t s p r o p e r t i e s w i t h r e s p e c t  to n a t u r a l l y e l i c i t e d  states.  D e f i n i t i o n s and t h e o r i e s . The  c o n c e p t s o f emotion and m o t i v a t i o n a r e complex and t h e d i f f i -  c u l t y o f p r o v i d i n g an adequate d e f i n i t i o n has been q u i t e a p p a r e n t i n r e c e n t r e v i e w s (Brady, 1960; Grossman, 1967; G o l d s t e i n , 1968).  Of  p a r t i c u l a r i n t e r e s t here i s a c o n c e p t t h a t i s r e l e v a n t t o how an o r ganism s u r v i v e s i n i t s e n v i r o n m e n t . have t h r e e components:  Most t h e o r e t i c a l e x p l a n a t i o n s  i n i t i a t i n g s t i m u l i , c e n t r a l s t a t e , response.  For each t h e o r y , t h e d e f i n i t i o n f o l l o w s from the emphasis p l a c e d on one o r more components. (a)  Emotion. There have been d e f i n i t i o n s o f emotion i n ages p a s t .  (1970) i n a h i s t o r i c a l r e v i e w  Bindra  o f e m o t i o n , and Masserman (1941) i n h i s  i n t r o d u c t i o n have i n d i c a t e d t h a t s i n c e the Greek p h i l o s o p h e r s ,  man  has been aware o f h i s " p a s s i o n s " and has a t t e m p t e d to l o c a l i z e them  - 2-  to such regions as the heart, the pineal body or the v e n t r i c l e s . The modern story of emotions i s considered by most people to begin with the ideas of William James which were published i n his "Principles of Psychology" i n 1890.  He recognized that emotion had two  aspects:  the e x p e r i e n t i a l and the expressive; the former being the subjective f e e l i n g s , the l a t t e r the.autonomic and somatic changes. component of the theory was the order of events was:  the "exciting f a c t " .  third  According to James  e x c i t i n g f a c t , expression, experience.  a c o u n t e r i n t u i t i v e approach ensured for years to come.  The  Such  that the theory would be remembered  A similar peripheral theory of emotion was  posed by Carl Lange at the same time.  pro-  These theories are known c o l l e c -  t i v e l y as the James-Lange theory and the implications of i t are a matter of controversy (Fehr and Stern, 1970; Although minology and  James  1  o r i g i n a l formulation was  still  V a l i n s , 1970). i n i n t r o s p e c t i v e ter-  thus untestable, considerable research i n v o l v i n g p e r i -  pheral manifestations of emotion was  stimulated.  This research neces-  s a r i l y involves human subjects because a verbal report as to how subject " f e e l s " i s needed.  the  Yet due to possible confusion between the  concepts of experience and expression, or a disregard for the d i f f e r e n c e , many experimenters  have inferred the presence of a f f e c t i n animal sub-  jects (Goldstein, 1968).  I t i s clear then that animals  should not be  used as subjects i n experiments testing the theory that emotional perience i s due  ex-  to the feedback of peripheral behavioural information.  The central mechanisms of emotional experience and have been accented  i n several theories.  expression,  Cannon (1927, 1931)  brought  - 3 -  out a t h a l a m i c t h e o r y as an a l t e r n a t i v e Cannon r e c o g n i z e d t h a t e x p e r i e n c e and attributing  these  to a c t i v i t y  to t h a t of James-Lange.  e x p r e s s i o n were s e p a r a t e ,  i n the thalamus.  He  thalamus as a " c e n t e r " of emotion which added an to the incoming  s e n s o r y s t i m u l i on t h e i r way  through One  autonomic and  somatic  "emotional  Dis-  the e x p r e s s i o n to  pathways near  the hypothalamus.  of the main p o i n t s of Cannon's t h e o r y i s the c o r t i c a l i n -  h i b i t i o n of the thalamus.  Arnold  (1950, 1960)  t h i s as b e i n g an e x c i t a t o r y c o n n e c t i o n .  c e n t r a l and  she attempts  saw  considerably  to r e c o n c i l e not o n l y  time.  Hebb's t h e o r y i s even more s p e c u l a t i v e  and h y p o t h e t i c a l than A r n o l d ' s , and findings  a c o n s i d e r a b l e amount a t t h a t  to a t t r i b u t e v a r i o u s e m o t i o n a l r e a c t i o n s to  s p e c i f i c p a r t s of the b r a i n .  experimental  theory,  p e r i p h e r a l t h e o r i e s ( i . e . James-Lange) but a l l the e x p e r i -  mental e v i d e n c e , of which t h e r e was Furthermore,  i n her  T h i s t h e o r y was  more complex than Cannon's s i n c e i t attempted  L i n d s l e y ' s accounts  ( G o l d s t e i n , 1968).  b e t t e r the  Hebb f o r m u l a t e d a  about h y p o t h e t i c a l n e u r a l mechanisms which when d i s r u p t e d emotion.  quale"  to the c o r t e x .  i n h i b i t i o n of the thalamus by the c o r t e x caused occur  p o s t u l a t e d the  Lindsley's activation  t h e o r y summarizes the  between the e l e c t r i c a l a c t i v i t y of the b r a i n and  Papez was  produced  relationship  emotional a r o u s a l .  B e s i d e s Cannon's t h e o r y , the most i n f l u e n t i a l has been t h a t of James Papez (1937).  theory  t h e o r y of emotion  an a n a t o m i s t  and  while  l o o k i n g f o r a r e l a t i o n s h i p among the s t r u c t u r e s i n the m e d i a l w a l l of the hemispheres f o r m u l a t e d a r e l a t i o n s h i p between these s t r u c t u r e s  - 4 -  and  the a v a i l a b l e e v i d e n c e on emotion.  He  c o n s i d e r e d the c o r t e x o f  the c i n g u l a t e gyrus as the p l a c e m e d i a t i n g e m o t i o n a l e x p e r i e n c e . impulses reached  the c i n g u l a t e gyrus by way  went out a g a i n the same way. p r e s s i o n o f emotion was  o f the hypothalamus  The r o l e of the hypothalamus i n the  i n v o l v e d i n emotional experience.  (1949) e n l a r g e d the a n a t o m i c a l bounds of Papez's concept t h a t the hypothalamus was  suggested  an e s s e n t i a l p a r t of the e f f e c t o r  system  or  "visceral brain"  as he c a l l e d  t h a t the c e n t r a l gray o f the b r a i n s t e m was  on the l i m b i c system w i t h r e g a r d to e m o t i o n a l The  experiments  better  1960).  agreed mechanism as p a r t  i t , MacLean  derived at  These t r a n s e c t i o n s produced  I t seemed t h a t as one  de Barenne and  Bard  emotional behaviours Bucy  The  progressed r o s t r a l l y  (1928) determined  Cannon  than w i t h o n l y the midi n the b r a i n became  t h a t the s t r u c t u r e e s s e n t i a l f o r  w e l l c o o r d i n a t e d and d i r e c t e d rage behaviour was  and  first  rage r e s p o n s e s which were  stem, the autonomic components, a t l e a s t , o f the rage response more complete.  (1955)  "interdependent"  o b s e r v a t i o n s on man.  S h e r r i n g t o n , Dusser  i n t e g r a t e d w i t h the d i e n c e p h a l o n i n t a c t  brain intact.  MacLean  were t r a n s e c t i o n s o f the b r a i n s t e m a t v a r i o u s l e v e l s  done by G o l t z , Woodworth and (Brady,  ex-  processes.  e v i d e n c e f o r a l l these c e n t r a l t h e o r i e s was  from a b l a t i o n s t u d i e s on animals and c l i n i c a l first  and  In a d d i t i o n to the s t r u c t u r e s commonly r e g a r d e d  of the l i m b i c  and  emphasized i n a d d i t i o n to i t s many r e c i p r o c a l  c o n n e c t i o n s to s t r u c t u r e s  of emotion.  The  the hypothalamus.  Other  as the r e s u l t of a b l a t i o n were r e p o r t e d by K l u v e r  (1939) f o r temporal  lobe l e s i o n s  i n monkeys.  There were many  - 5 -  other  examples of b o t h l i m b i c and  cortical  s t r u c t u r e s which when  removed or damaged produced changes i n behaviour and  emotionality  (Grossman, 1967). Further was  derived  stimulated provide  e v i d e n c e f o r the r o l e of b r a i n s t r u c t u r e s i n emotion  from s t u d i e s i n which d i s c r e t e a r e a s of the b r a i n were electrically.  information  winner W.  R.  on  Hess (1954).  stimulating effects.  technique which has  the b r a i n was  h i s coworkers were a b l e  duce, on  This  By  localizing  to map  The  popularized  by  done so much to the Nobel P r i z e  the e l e c t r o d e  most of the b r a i n w i t h  hypothalamus and  s t i m u l a t i o n , r e s p o n s e s such as  t i p , he respect  f e a r and  not o n l y e m o t i o n a l r e s p o n s e s such as r a g e and t i o n a l behaviour such as f e e d i n g , d r i n k i n g and  (b)  anger.  prosub-  produced  f e a r but a l s o m o t i v a copulating  (Grossman,  Thompson, 1967).  Motivation.  have been c o n s i d e r e d as hunger, t h i r s t , Emotions tend  conceptually apart  sexual  d e s i r e and  i r r e g u l a r l y due  and  construct  has  from m o t i v a t i o n a l  m a t e r n a l care  to be u n o r g a n i z e d , i n v o l v e h i g h  proposed a theory  called  depression,  states  (Bindra,  Bindra  has  than d i f f e r e n c e s between the to e x p l a i n them on  " c e n t r a l motive s t a t e " .  such  1969).  l e v e l s of a r o u s a l  to chance e x t e r n a l f a c t o r s .  t h a t there are more s i m i l a r i t i e s cepts  the  T h i s and  In the p a s t e m o t i o n a l s t a t e s such as anger, f e a r , j o y ,  occur  to  v i c i n i t y were found to  sequent s t u d i e s found t h a t s t i m u l a t i o n of the hypothalamus  1967;  and  and  shown two  con-  the b a s i s of a common  - 6 -  The current view i s to consider emotion as a s p e c i a l class of motivated behaviour (Milner, 1970).  Milner defines motivation as  "certain hypothetical states of the nervous system that determine what actions the organism w i l l perform at any moment" (p. 297). The example given i s of a dog which eats because i t i s hungry. Hunger, the c e n t r a l state, i s a form of motivation i n this  case.  Another example i s a dog which runs because i t i s a f r a i d .  Fear i s  the c e n t r a l state and i s a form of motivation.  This c e n t r a l state  can be operationally defined by quantifying the actions of the animal when i t obtains food or runs to a safe place.  As with emotion, there  i s a tendency to imply a c e n t r a l subjective state i n addition to any behavioural meaning.  Milner suggests that the term emotion should be  reserved for the introspected central states with the hope that the d i f ference between subjective state  and overt behaviour would be made  clear by the terminology. Stellar's (1960) view of motivation i s i n terms of drive, goaldirected a c t i v i t y and s a t i a t i o n .  Satiety i s the reduction of motivated  behaviour following the achievement of a goal. of motivated behaviour.  Drive i s the i n t e n s i t y  The other term i s self-explanatory.  The experi-  mental measure of these involves consummatory behaviour under various conditions.  This terminology  has been developed because the t y p i c a l  examples of consummatory behaviour have been eating and drinking.  The  concept has been extended to include also such behaviour as the avoidance of noxious stimulation.  - 7 -  S t e l l a r has suggested a neural mechanism for motivated behaviour. His e a r l i e r theory This i s due  (1954) stresses heavily the r o l e of the hypothalamus.  to the strong evidence for a l a t e r a l excitatory and medial  i n h i b i t o r y hypothalamic system i n the regulation of food intake.  Stellar,  using this model, generalized i t to include other motivated behaviour and added enough factors to make i t work and account for a v a i l a b l e evidence. His more recent paper (1960) r e i t e r a t e s the r o l e of the hypothalamus and acknowledges even more factors which act on the system. factors i s learning, and how ciated with the arousal of  One  of these  previously neutral s t i m u l i can become assomotivation.  The r o l e of s t i m u l i i n motivation has yet to be considered. addition to behaviour, which can be measured, and t r a l state defined as motivation  the hypothetical cen-  by this measurement there i s a  (or stimuli) which i n i t i a t e s them.  In  stimulus  Some theories explain emotion and  motivation on the basis of the s t i m u l i which e l i c i t them.  Hammond (1970)  s p e c i f i e d these s t i m u l i as either rewards or punishments or the absence of them.  They can also be s t i m u l i which can predict the occurrence of  reward or punishment.  This i s accomplished by learning.  The responses  produced by such s t i m u l i are c l a s s i f i e d as either approach or withdrawal. The neural basis of such a theory has been well investigated since the discovery  (Olds and Milner, 1954;  ICS i s rewarding or  Olds, 1962)  of areas of the brain where  punishing.  Another view of emotion and motivation has been proposed by ethologists and some investigators of the neural aspects of behaviour.  Their  - .8 -  basic ideas are the same but the terminology i s d i f f e r e n t .  Brown (1969)  questions the usefulness of the term "emotion" to describe behaviour i n animals such as j e l l y f i s h , insects'or frogs (for example) even though such behaviour may be f u n c t i o n a l l y equivalent to a human's. have some mechanisms which enable them to survive i n their The simplest mechanism i s a r e f l e x .  A l l animals environment.  I t i s an important determinant of  behaviour i n animals with primitive nervous systems.  In animals higher  i n the phylogenetic scale, with better developed nervous systems, complex adaptive behaviours occur i n addition to simple r e f l e x e s .  Within a given  species these behaviour patterns are consistent and the name speciest y p i c a l behaviour has been applied to them. The study of behaviour i n a wide range of species has helped the understanding of the neural organization of such behaviour.  Just as the  nervous system gets more complex as you go up the phylogenetic scale, so i t does when you go from lower to higher l e v e l s i n a given species (Brown, 1969).  The example c i t e d by Brown i s the stimulation of a motor neuron  i n the Octopus, giving an arm movement.  Stimulation at progressively  higher levels gives movement of a l l arms, placing arms i n attention p o s i t i o n , and f i n a l l y the attention p o s i t i o n including other parts of the body.  Another example i s the previously mentioned  studies on brain  transected animals which indicated progressively greater organization of behaviour from the s p i n a l cord up to the forebrain.  The best examples,  however, have come from the behaviours produced by the e l e c t r i c a l  sti-  mulation of l o c a l i z e d areas of the brain i n animals from bullfrogs to  - 9 -  man (Doty, 1969).  Here complex b e h a v i o u r s produced by ICS have  e a t i n g , d r i n k i n g , gnawing, h o a r d i n g , a t t a c k , c a r r y i n g and m a t e r n a l behaviour  sexual  behaviour,  included object  ( V a l e n s t e i n , Cox and K a k o l e w s k i , 1969,  1970).  R e s e a r c h l e a d i n g to the p r e s e n t  investigation.  E a r l y attempts a t o u t l i n i n g the n e u r a l mechanisms o f b e h a v i o u r involved  s t i m u l a t i o n o f the b r a i n w i t h o b s e r v a t i o n  identifying  the s t i m u l a t i o n s i t e s , maps were made and s t r u c t u r e s  f i e d with p a r t i c u l a r e f f e c t s .  (a)  identi-  the q u a n t i f i c a t i o n o f  induced behaviour and then to the a p p l i c a t i o n of l e a r n i n g p r i n c i p l e s . Description:  e f f e c t s and l o c a t i o n .  In 1927, W. R. Hess r e p o r t e d e m o t i o n a l behaviour  h i s discovery  o f c e n t r a l l y induced  to the German P h y s i o l o g i c a l S o c i e t y  (Akert,  I t was c l e a r then t h a t e l e c t r i c a l s t i m u l a t i o n o f a d i s c r e t e area brain could  initiate  the n e u r a l  of complex motor b e h a v i o u r . able  By  Concern over whether c e r t a i n e f f e c t s  resembled n a t u r a l b e h a v i o u r or n o t l e a d to f i r s t ICS  o f the e f f e c t s .  a c t i v i t y involved  Hess c a l l e d  1961). o f the  i n the c o o r d i n a t i o n  i t a f f e c t i v e d e f e n s e and was  to c o r r e l a t e i t with b r a i n s t r u c t u r e s .  I n the r e g i o n o f the p e r i -  f o r n i c a l n u c l e u s i n c a t s near the d e s c e n d i n g column o f the f o r n i x i n the hypothalamus, he o b t a i n e d  a defense r e a c t i o n which resembled the  behaviour o f a normal c a t c o n f r o n t e d  by a dog.  I t included  assumption  of a defense p o s i t i o n , angry v o c a l i z a t i o n s , r e t r a c t i o n of the e a r s , d i l a t a t i o n o f p u p i l s , h i s s i n g , s p i t t i n g and a w e l l d i r e c t e d  attack.  - 10 -  Other components are lashing t a i l , unsheathing claws, defecation, urination, s a l i v a t i o n , p i l o e r e c t i o n , sweating of the footpads, respiratory a c t i v a t i o n and r e t r a c t i o n of the n i c t i t a t i n g membrane (Akert, 1961).  Not obvious i n the unanesthetized, behaving animal are muscle  d i l a t a t i o n , increased blood pressure and vasoconstriction of blood vessels i n skin and intestines (Abrahams, H i l t o n and Zbrozyna,  1960).  Hunsperger (1956) using Hess' method investigated more f u l l y these a f f e c t i v e reactions, extending the anatomical boundaries discriminating more d e t a i l s of the behaviour.  and  He distinguished bet-  ween a f f e c t i v e defense, as described above, and f l i g h t , which has many of the same components but leads to running instead of attack. A f f e c t i v e defence was obtained from two c e n t r a l zones:  the p e r i f o r n i -  c a l region of the r o s t r a l hypothalamus as described above, and the middle portion of the midbrain central gray.  These two zones are  embedded i n an unbroken f i e l d extending from the gray matter of the preoptic area back to central gray of the midbrain. pheral zone the f l i g h t reaction i s obtained.  From this p e r i -  This simple c o r r e l a t i o n  of stimulation locus with stimulation e f f e c t i s complicated by the strength of stimulation v a r i a b l e .  There are mixed effects at the  borders of these zones, of course, but an increase of voltage w i l l tend to reverse the threshold behaviour. central zones may  Strong stimulation of the  cause the cat to suddenly jump off the table, and  strong stimulation of the peripheral zone can evoke an a f f e c t i v e defence reaction.  - 11 -  Subsequent papers by Hunsperger (Fernandez de Molina and Hunsperger, 1959, 1962; Hunsperger, 1963) have r e i t e r a t e d h i s view of the organization of a f f e c t i v e reactions and have extended the system into the amygdala.  He has also attempted to resolve the mixed e f f e c t s  into their components by using threshold stimulation and a very small stimulation electrode  (Brown, Hunsperger and Rosvold, 1969a,b).  Using  this method, a growling reaction, a h i s s i n g reaction and two types of f l i g h t were produced.  His f l i g h t type "a" i s characterized by the cat  looking about "as i f i n search of an e x i t " and then jumping from the table.  F l i g h t type "b" consists of exploration and s n i f f i n g of the  surroundings followed by jumping off the table. "b" were obtained  from the intermediate  thalamus r e s p e c t i v e l y .  Suprathreshold  F l i g h t types "a" and  zone and caudo-lateral hypostimulation s t i l l gave mixed  e f f e c t s but they conclude that the predominant c h a r a c t e r i s t i c of the response depends on the stimulation locus. Yasukochi (1960) obtained  a type "a" f l i g h t response from the  anterior hypothalamus which he l a b e l l e d as fear or anxiety. type "b" response was obtained  A flight  from the posterior hypothalamus.  This  behaviour i s s u f f i c i e n t l y vague that several words could describe i t . Yasukochi uses "yearning" or " c u r i o s i t y " . when stimulated  He notes that some cats  i n a "fear" region would attempt to escape through  any small hole i n their cage.  Glusman and Roizin (1960) also describe  f l i g h t responses which include c a r e f u l l y organized  attempts to escape  - 12 -  from an enclosure i f an opening was  provided.  Some animals also  searched and explored the cage before escaping. i n t e n s i t i e s an aggressive response was  At higher current  changed to "violent panicky  f l i g h t " , a r e s u l t similar to Hunsperger's.  Also i n agreement with  him were the h i s t o l o g i c a l l o c a l i z a t i o n of the stimulating electrodes. Romaniuk (1963, 1965, i n two respects.  1967) disagreed with the above formulation  He did not obtain f l i g h t from high i n t e n s i t y stimu-  l a t i o n of a rage point.  Only the latency and i n t e n s i t y of the response  were changed and not the nature of the response.  He also did not ob-  tain the same l o c a l i z a t i o n within the hypothalamus. ventral d i v i s i o n between f l i g h t and rage.  This was  He found a dorsale s p e c i a l l y prominent  i n the medial hypothalamus where the t y p i c a l rage response i s obtained from the ventromedial nucleus. Both the hypothalamus and midbrain were investigated by.Skultety (1963), i n an attempt  to r e p l i c a t e Hunsperger's 1956 r e s u l t s .  i s defined as "agitated scurrying about the box" and attempts out of the box.  Flight to get  These e f f e c t s were obtained from the hypothalamus but  not from the r o s t r a l midbrain, below the superior c o l l i c u l u s .  Flight  was obtained, however, from the central gray i n the caudal midbrain. I t was  characterized only by attempts by the cat to escape from the  apparatus.  There were no searching movements.  In the experiments been the cat.  reported so f a r , the experimental animal has  Although patterns of aggressive-defensive behaviour  can  - 13 -  be o b t a i n e d by e l e c t r i c a l  s t i m u l a t i o n o f the b r a i n s o f f r o g s ,  alliga-  t o r s and w i l d ducks (Doty, 1969) the. d i s c u s s i o n w i l l be r e s t r i c t e d t o mammals.  An e x p l o r a t o r y e s c a p e - l i k e l o c o m o t i o n w i t h elements  of a „  s e a r c h f o r an escape r o u t e was o b t a i n e d i n the opossum by R o b e r t s , S t e i n b e r g and Means (1967).  T r a c z y k ( c i t e d i n B a l i n s k a , Romaniuk and  Wyrwicka, 1964) o b t a i n e d a f l i g h t r e a c t i o n by s t i m u l a t i n g the hypothalamus  of r a b b i t s .  R a b b i t s have a l s o been used i n t h e s t u d y o f drugs  on ICS i n d u c e d a g g r e s s i v e - d e f e n s i v e r e a c t i o n s (Val'dman and K o z l o v s k a y a , 1970;  Silvestrini,  dogs by Fonberg  1958).  (1967).  F e a r , d e f e n s e and rage have been o b t a i n e d i n I n the monkey, Delgado, R o s v o l d and Looney (1956)  described a fear response. g r a y o f the m i d b r a i n .  One o f t h e i r e l e c t r o d e s was near the c e n t r a l  I n man t h e r e have been many r e p o r t s o f s u b j e c t i v e  e m o t i o n a l e x p e r i e n c e s from s t i m u l a t i o n o f many a r e a s o f the b r a i n .  For  example, Sano e t a l (1970) have r e p o r t e d f e e l i n g s o f i n t e n s e h o r r o r on s t i m u l a t i n g the p o s t e r i o r hypothalamus.  S p i e g e l , K l e t z k i n and S z e k e l y  (1954) and N a s h o l d , W i l s o n and S l a u g h t e r (1969) summarize r e p o r t s o f p a i n on s t i m u l a t i o n o f t h e m i d b r a i n tectum and c e n t r a l g r a y .  Heath and  M i c k l e (1960) r e p o r t a n x i e t y and d i s c o m f o r t f r o m t h e r o s t r a l hypothalamus and t e n s i o n and rage from t h e c a u d a l d i e n c e p h a l o n and m e s e n c e p h a l i c mentum.  teg-  I n r a t s rage type r e s p o n s e s have been d e s c r i b e d t o a g r e a t ex-  t e n t ( f o r example, Panksepp and T r o w i l l , 1969; Panksepp, 1971) b u t explicit  d e s c r i p t i o n s o f a f l i g h t response a r e d i f f i c u l t t o f i n d .  The  f l i g h t r e s p o n s e , i n the form d e s c r i b e d i n c a t s does appear i n e x p e r i m e n t s where the hypothalamus o f the r a t i s s t i m u l a t e d f o r some o t h e r  purpose.  - 14 -  In that case f l i g h t i s l a b e l l e d under the general heading of "other effects" (b)  (Woodworth, 1971;  Vergnes and K a r l i ,  1970).  Quantification of ICS behaviour. The terminology used has varied from author to author.  Such  terms as alarm reaction, rage, aggressive-defensive reactions, a f f e c tive defense, attack, threat, f l i g h t , fear, escape, agonistic behaviour, emotional reactions, species s p e c i f i c defence reaction and stimulusbound behaviour have a l l been used to describe the r e s u l t s of stimul a t i n g the hypothalamus, mesencephalon and other parts of the brain. Some responses are so general that there are a host of words to describe it.  This i s true for the s n i f f i n g , exploration, c u r i o s i t y , general ac-  t i v i t y and general locomotion obtained at most points i n the hypothalamus.  There i s obviously a need to evaluate and quantify these behaviours  systematically.  This i s done by providing suitable environmental objects  on which the animal can act.  A simple example i s eating produced by the  a v a i l a b i l i t y of food coupled with hypothalamic stimulation (Margules and Olds, 1962). A similar example has already been provided with respect to a f f e c tive behaviour.  I t i s noted i n most papers that the cat, besides looking  ferocious, w i l l also attack the experimenter or a stuffed model cat (Brown et a l , 1969a,b).  S i m i l a r l y with f l i g h t , part of the d e f i n i t i o n  i s that the animal w i l l attempt means a v a i l a b l e .  to escape from wherever i t i s by whatever  This can be observed i n almost any test s i t u a t i o n but  i t i s s t i l l a crude method of evaluating behaviour.  - 15 -  It i s usually s u f f i c i e n t to characterize the e f f e c t s of ICS by providing an environmental object on which the animal can act. The strength of response can be measured and i s usually the time required for a particular response.  Wasman and Flynn (1962) for  example provided their cats with a r a t to attack.  The latency to  i n i t i a l movement and attack latency were recorded.  In addition, the  attack behaviour was rated by the experimenter and an independent observer, a technique used by Roberts (1958 a) into alarm and f l i g h t groups.  to separate his cats  Renfrew (1969) provided h i s monkeys  with a rubber hose to attack and the number of bites made was automatically recorded. The measure of f l i g h t has been done s i m i l a r l y .  The animal i s  provided with a means of escape and the latency to do so i s recorded. In the same manner as for attack, the latency to i n i t i a l movement may be recorded (Siegel and Skog, 1970) or the time required to perform a certain response may be recorded. ponses used:  There have been three basic res-  shuttle-box running, maze running, and plate-pushing.  Coupled with these, many studies have also determined the threshold current necessary to produce a response or have studied the e f f e c t of stimulus parameters  (Renfrew, 1969; Bower, 1959).  The most common method of measuring f l i g h t i s the use of a two compartment box or shuttle-box. F l i g h t i s then defined as the crossing of  the barrier between the two compartments.  A system of photo-cells  - 16 -  can then detect the crossing and with a clock i n the c i r c u i t , can measure escape latency and terminate ICS (Stokman and Glusman, 1968). This method has been used with cats by Stokman and Glusman (1969,  1970),  Roberts (1958a,b), Cohen, Brown and Brown (1957), and Brown and Cohen (1959);  and with rats by Stein (1965), Mogenson (1962), Cox (1967),  and Wolfle et a l (1971).  Another method i s to provide a runway or  maze through which the cat (Roberts, 1958a,b) or r a t (Bower and M i l l e r , 1958) can escape.  Again, appropriate use of photo-cells allows the  measurement of running time and also terminates ICS. Delgado, Roberts and M i l l e r  (1954) trained their cats to escape  from foot shock by r o t a t i n g a paddle wheel and then substituted ICS for foot shock.  Nakao (1958) used this method but instead of the  wheel used a paddle covering a hole i n the testing chamber.  He noticed  that cats which had not been pretrained with foot shock would press the paddle to terminate ICS only i f they showed manifestations of f l i g h t . They learned to push the paddle after a c c i d e n t a l l y pushing i t i n attempting to escape from the box.  Nakao obtained paddle-pushing from  sti-  mulation of f l i g h t areas i n the hypothalamus and i n the midbrain (Nakao, Yoshida and Sasaki, 1968).  Using the same plate-pushing technique, also  in cats, Wada and Matsuda (1970) and Wada et a l (1970) found that not a l l points that produced f l i g h t or escape behaviour would, on testing i n the plate box, lead to plate-pushing. Therefore a d e f i n i t i o n of f l i g h t based on the plate-pushing task i s more exclusive since i t e l i minates responses such as general locomotion which would not be excluded  - 17 -  i n a shuttlebox or runway task.  I t has not yet been determined i n  the r a t how many points giving similar behaviour are capable of producing a plate-pushing response.  (c) Conditioning. Most investigators have implied, on the basis of their observations and/or measurements of ICS induced behaviours, that they are not merely stereotyped motor acts but are the outcome of a c e n t r a l motivational state.  One of the properties of motivated behaviour i s  that i t can be influenced by learning.  This enables an animal, f o r  example, to avoid a s i t u a t i o n that has been previously associated with some danger (Milner, 1970).  To further characterize the pro-  perties of ICS induced behaviours there have been numerous attempts to condition them to neutral s t i m u l i , and to compare the r e s u l t s of ICS with "natural" motivational s t i m u l i such as footshock.  The o r i -  g i n a l purpose i n doing so was to determine whether or not ICS produced an emotional experience i n addition to emotional behaviour  (Masserman,  1941). Masserman (1941, 1943) reasoned that i f ICS of the hypothalamus was accompanied by a meaningful subjective experience then the animal could learn to respond to a signal which predicted the occurrence of ICS.  After numerous pairings of various stimuli with hypothalamic ICS  he succeeded  i n conditioning only some autonomic e f f e c t s i n some cats  even though ICS was producing rage responses. of ICS he did obtain a conditioned response.  Using footshock instead Since Masserman's work  - 18 -  there have been several studies which have and have not obtained conditioning of ICS induced behaviour. In contrast to Masserman's findings, p a i r i n g of ICS with neutral s t i m u l i has produced a conditioned response to the stimuli alone (Nakao, 1958).  I t has also been noticed that dogs showed conditioned responses  to the apparatus after r e c e i v i n g hypothalamic stimulation i n i t (Fonberg, 1967).  Cats have shown active avoidance of a d i s t i n c t i v e compartment  where they received ICS and have shown passive avoidance of a food tray (Nakao, 1958; Delgado et a l , 1954).  Ross et a l (1965) on pairing mid-  brain ICS i n cats with a tone or c l i c k s obtained f i r s t an a t t e n t i o n a l and then an emotional conditioned response which resembled f l i g h t obtained from the hypothalamus.  In a l l of these s i t u a t i o n s , the animal  has no control over the occurrence of ICS. The more t y p i c a l experimental s i t u a t i o n , as discussed above, i s to have some action of the animal terminate (escape from) ICS.  The  animal can then be provided with a warning stimulus ( b e l l , l i g h t , etc.) to see i f i t can avoid ICS by responding to the warning stimulus. Fonberg  (1967) found that dogs would avoid ICS producing " f e a r - f l i g h t "  but not rage by performing a leg f l e x i o n during the warning stimulus. Romaniuk (1964) stimulating f l i g h t points i n cats obtained the conditioned avoidance response of r a i s i n g on their hind legs.  Ross et a l  (1965) i n addition to the unavoidable ICS s i t u a t i o n discussed previously, allowed their cats to avoid ICS by producing an "emotional conditioned response" to a warning s i g n a l .  - 19 -  Using a shuttle-box response (Cohen et a l , 1957; Brown and Cohen, 1959) or paddle-wheel turning (Delgado et a l , 1954), avoidance to ICS was obtained.  Roberts (1958a) using both a shuttle-box  and T-maze obtained avoidance from "alarm" points but not from f l i g h t points.  Stokman and Glusman (1970) also f a i l e d  from f l i g h t points i n the hypothalamus. failed  to obtain avoidance  Wada and Matsuda (1970)  to obtain avoidance from hypothalamic ICS i n a plate-pushing  s i t u a t i o n whereas Nakao (1958) did obtain i t .  Wada et a l (1970) noted  a difference between hypothalamic and midbrain ICS i n i t s a b i l i t y to produce avoidance. In r a t s , only Mogenson (1962) was able to obtain two-way active avoidance.  Even then only two of his three animals would do i t .  Wolfle et a l (1971) obtained some one-way avoidance but not two-way. Stein (1965), Cox (1967) and Johnson and Levy (1969) also f a i l e d to obtain two-way shuttle-box avoidance with either hypothalamic or midbrain ICS.  In a T-maze s i t u a t i o n Bower and M i l l e r  (1958) found that  rats remained i n the s t a r t box u n t i l the onset of hypothalamic ICS. Since r a t s have not been trained to date on a plate-pushing task i t i s not known whether this measure of " f l i g h t " would produce avoidance i f a warning stimulus was provided. A current explanation for f a i l u r e  of an animal to avoid a s t i -  mulus that i t w i l l terminate has been proposed by Roberts  (1958a).  He proposed that the onset of ICS was rewarding and that i t s continuation became aversive.  Therefore the animal would be rewarded for  - 20 -  waiting for ICS onset and then would r a p i d l y turn i t o f f to avoid punishment.  Roberts tested this hypothesis (1958b) and provided  some support for his view.  Bower and M i l l e r  (1958) pretested their  rats with several measures of rewarding ICS e f f e c t s and found on subsequent avoidance t r a i n i n g a f a i l u r e to avoid.  Brown and Cohen  (1959) however, obtained both approach and avoidance at the same hypothalamic s i t e , a r e s u l t contrary to that predicted by Roberts' hypothesis.  Their ICS e f f e c t s were similar to that which Roberts  describes as "alarm" and which he found produced avoidance and showed l i t t l e reward e f f e c t s .  Roberts admits  (1958b) that there i s  considerable overlap i n reward areas and f l i g h t areas. Nevertheless, i t seems that f l i g h t areas tend also to be rewarding. That this i s an o v e r s i m p l i f i c a t i o n i s shown not only by experiments where approach could not be obtained from points that did not produce avoidance (Wada and Matsuda, 1970) but also from the r e s u l t s • of stimulating the midbrain.  Although there are some reports of reward  areas i n the midbrain (Cooper and Taylor, 1967; Mayer et a l , 1971), the area i n and around the c e n t r a l gray i s considered to be involved with pain and aversion (Olds and Olds, 1963; Routtenberg, 1970; Spiegel et a l , 1954).  If Roberts' hypothesis were true, and i f midbrain stimulation  i s aversive, then there would be more reports of avoidance of midbrain ICS.  - 21 -  (d)  Summary. A v a r i e t y of behaviours  described as emotional  or motivational  have been produced by ICS presumably by d i r e c t a c t i v a t i o n of neurons involved i n the postulated c e n t r a l state which governs natural behaviour.  One such behaviour has been described as f l i g h t .  I t can  be e l i c i t e d from areas of the hypothalamus (HYP) and midbrain (MB) of cats.  In addition to some autonomic e f f e c t s , the main c h a r a c t e r i s -  t i c of this behaviour i s the search for an exit from an enclosure. This part of the behaviour pattern has been used to measure ICS induced f l i g h t by means of an enclosure with a small hole. to get out the ICS i s terminated  (escape).  i s provided the cat may or may not terminate  When the cat t r i e s  When a warning s i g n a l (WS) the WS  (avoidance).  Since there i s some controversy i n the l i t e r a t u r e over the properties of HYP and MB ICS that produce f l i g h t and since the plate-pushing method has not been applied i n species other than the cat, the present study was undertaken to determine the following: 1.  Description of f l i g h t i n rats produced by HYP and MB ICS.  2.  Quantification of the f l i g h t response using a platepushing task.  3.  Determine i f the r a t w i l l avoid HYP and/or MB ICS.  4.  Test the Roberts hypothesis using a s e l f - s t i m u l a t i o n task.  5.  Anatomical organization of f l i g h t behaviour as defined above.  - 22 -  METHOD Subjects. The subjects (S) were 30 male and female hooded rats obtained from Blue Spruce Farms (New York).  They were housed i n d i v i d u a l l y i n  an airconditioned (25°C) room with a 12-12 light-dark cycle. (Purina Rat Chow) and water were a v a i l a b l e ad l i b i t u m .  Food  At the time  of surgery their weight was 250-400 grams. Surgery. The electrodes were s t a i n l e s s s t e e l wires  (0.19 millimeters  diameter) insulated with glass c a p i l l a r y tubing after the method of Nakao (1958). mately 0.30 mm.  Overall diameter of the insulated electrode was approxiOnly the cross section of the t i p was exposed. A l l  electrodes were checked for i n t e g r i t y prior to implantation. The rats were anesthetized with Nembutal (60 mg/kg) and placed i n a Kopf stereotaxic instrument.  After exposing  the calvarium, four  s t a i n l e s s s t e e l machine screws were i n s t a l l e d as anchors for the dental cement.  One to four electrodes were then implanted  at various HYP and  MB s i t e s chosen from the atlas of Konig and K l i p p e l (1963).  A wire  attached to one of the anchoring screws was the i n d i f f e r e n t electrode. The electrode wires were then joined to amphenol male pins (220-P02) embedded i n an amphenol connector was  The e n t i r e assembly  molded into the completed plug through the use of dental a c r y l i c  cement. was  s t r i p (221-1260).  Aseptic technique was used throughout; post-operative  uneventful and no i n f e c t i o n was noticed.  allowed before  testing.  recovery  At least one week was  - 23 -  Apparatus. Monopolar stimulation was provided by a Grass S 4  stimulator  set to deliver monophasic square wave pulses, 1 msec i n duration, at a rate of 100 pulses per second.  Voltages ranged from 0.5 to 3 volts (V)  with most values f a l l i n g between 0.8 and 1.5V. negative.  The depth electrode was  Stimulation was conducted to the animal by means of 5 l i g h t -  weight f l e x i b l e wires ending i n an amphenol connector s t r i p (221-1160) with amphenol female pins  (220-S02).  There were b a s i c a l l y 3 pieces of apparatus:  an observation chamber,  a plate-box for escape and avoidance and a s e l f - s t i m u l a t i o n box. For observation of ICS induced behaviour a large box (61 x 61 x 71 cm) was used i n i t i a l l y , followed by a smaller box (30 x 30 x 60 cm).  The small  box was enclosed on a l l sides and top with brown fibre-board except for a hinged Plexiglas front through which the S entered and l e f t . wires entered through a hole i n the roof of the box.  Electrode  For these obser-  vations the S was connected d i r e c t l y to the stimulator. The plate-box had the same composition and i n t e r i o r dimensions as the small observation box with the following modifications.  The P l e x i -  glas door was replaced by a one-way viewing mirror that was fixed as part of the w a l l . and out of the box.  The top of the box was then the only access into The top was tight f i t t i n g and was equipped with a  60 watt l i g h t bulb enclosed externally such that a l l the l i g h t was directed into the box through a piece of translucent paper.  High on  - 24 -  the w a l l o p p o s i t e  t h e m i r r o r was a 4 i n c h s p e a k e r .  The bottom o f  the box was a g r i d o f 1/8 i n c h b r a s s r o d s spaced 5/8 i n c h (1.58 cm) center  t o c e n t e r and r a i s e d about 2 cm above t h e f l o o r .  The main  f e a t u r e o f t h e box was a 4 x 4 cm window covered by a P l e x i g l a s p l a t e ( F i g u r e 1) l o c a t e d on t h e w a l l a d j a c e n t  to the m i r r o r .  The p l a t e was  f l u s h w i t h the i n s i d e w a l l and a movement o f t h e p l a t e outward o f about 0.6 cm c l o s e d a m i c r o s w i t c h .  When the S was i n the box t h e room  l i g h t s were o u t and t h e box l i g h t was on, e n a b l i n g observe S w i t h o u t  the experimenter t o  S b e i n g a b l e t o see o u t .  When S was b e i n g  tested for plate-pushing,  S was c o n n e c t e d t o t h e  s t i m u l a t o r v i a a s w i t c h i n g u n i t ( F i g u r e 2) w h i c h s t a r t e d b o t h t h e ICS and  a c l o c k ( I n d u s t r i a l Timer C o r p o r a t i o n )  plate-pushing  to the nearest  0.01 second.  w h i c h measured l a t e n c y f o r ICS c o u l d be stopped e i t h e r  by S p r e s s i n g t h e p l a t e o r by t h e e x p e r i m e n t e r . For  the a v o i d a n c e t r a i n i n g another s w i t c h i n g u n i t was used ( F i g u r e 3).  I t allowed  a 5 sec.(^Wj) f o l l o w e d by a 0.5 s e c . pause, f o l l o w e d by ICS f o r  up t o a p p r o x i m a t e l y  10 s e c .  The c l o c k measured from WS  The^WSy'were b e l l s , l i g h t s and c l i c k s . desk lamp t h a t was p l a c e d an e l e c t r i c  The l i g h t was a 60 w a t t  j u s t under the t o p o f t h e box.  (6v) d o o r b e l l p r o d u c i n g  s h e l f 1 meter away from the box.  onset.  100 d e c i b e l s .  The b e l l was  I t was p l a c e d on a  The c l i c k s were g e n e r a t e d by a Grass S 4  s t i m u l a t o r a t a r a t e o f 5 / s e c , a m p l i f i e d and f e d t o t h e speaker i n t h e box.  I n a l l cases the i n t e n s i t y was s u f f i c i e n t t o produce an i n i t i a l  s t a r t l e r e s p o n s e i n a l l S.  . 25  Figure 1  Side view of one wall of the plate box.  Shown i n  the clear p l a s t i c plate which when moved 0.6 cm to the r i g h t closes the switch.  Scale:  f u l l size.  Wall  4  cm  Plastic  plate  7 cm  Grid floor  o  o  o  o to counter  • 26  Figure 2  Semischematic diagram of the escape t r a i n i n g apparatus. The clock and ICS are started by the experimenter and terminated by S.  The number of ICS presentations i s  automatically counted.  from plate  Start  Stop }  Counter  to subject  Stimulator Switch Unit A  Clock  27  Figure 3  Seraischematic diagram of the avoidance t r a i n i n g The sequence 5 sec. WS,  apparatus.  0.5 sec. delay, ICS i s i n i t i a t e d  by s t a r t and i s terminated by a plate-push by S.  Timing  i s from WS onset and a l l plate-pushes are recorded.  Stop  Start  Counter Switch Unit B  2.  WS timer  light bell click  . 5 sec delay  Stimula tor  ICS timer  from plate to subject  - 28 -  The s e l f - s t i m u l a t i o n test again used the 30 x 30 x 60 cm f i b r e board box with a Plexiglas door and the addition of a bar 2 x 10 cm located 12 cm above the f l o o r i n the wall adjacent to the door.  Dep-  ression of the bar by 0.4 cm closed a switch which i n i t i a t e d a 0.25 sec. t r a i n of pulses from the stimulator. a Neuropsych Corporation u n i t .  Switching and timing was done by  Number of bar presses was recorded on  a d i g i t a l counter.  Procedure. (a)  Screening. After recovery from surgery S were brought to the testing area  on one or two occasions to f a m i l i a r i z e them with the procedure of connecting to the stimulator.  This f a c i l i t a t e d subsequent handling.  On  being placed i n the observation box a few minutes was allowed for exp l o r a t i o n , then ICS was administered s t a r t i n g with 0.5V and increasing i n 0.1V increments u n t i l the stimulation e f f e c t was characterized. Stimulation never exceeded 4V.  I f there were more than one electrode  per animal then the most anterior ones were tested f i r s t .  The stimu-  l a t i o n e f f e c t and the voltage producing i t were recorded.  I t was noted  that a l l of the e f f e c t s obtained i n the large observation box could be seen i n the small box.  Consequently,  most screening was done there.  Some of the later S's were screened d i r e c t l y i n the plate-box. (b)  Escape t r a i n i n g . After screening, S were tested i n the plate-box to see i f they  would escape from ( i . e . terminate) ICS by pushing the plate.  The  - 29  group  t e s t e d h e r e was  c l u s i o n of  S w h i c h showed no  m e n t s s u c h as lated  smaller  limb  head  made, t h e  ceeded  duration.  sec.  t e s t e d on  the  e f f e c t or  Various  a r e s p o n s e was 30  than the  t u r n i n g , eye  movements.  -  original only  g r o u p due  stereotyped  b l i n k i n g , c i r c l i n g movements o r current  t i m e was  i f i t became a n  established  whether  or n o t  the  p o n s e and  (c)  plate.  sessions the  i n order  threshold  for  Once t h e opportunity  restrials  s e l e c t i o n of  further training  to e s t a b l i s h a s t a b l e the r e s p o n s e .  ICS  res-  was  given  training. e s c a p e r e s p o n s e was to avoid  ICS.  The  being  presented alone at f i r s t  plate-pushing.  The  sec.  delay and  60  e a c h WS  sessions.  ICS  T h e r e was  order  o f WS  onset  to  the  was  modality  200  u s u a l l y at  and  trials  plate-pushing  r e s p o n s e was  that  o r MB  onset of  S was  l i g h t or  given 5/sec  they caused  ICS.  ICS.  There  Each  T r i a l s were g i v e n were g i v e n  l e a s t one  v a r i e d f r o m one  a bell,  to i n s u r e  constituted a t r i a l .  modalities  was  t h e n p a i r e d w i t h HYP  b e t w e e n o f f s e t o f WS  t a t i o n o f WS For  WS  produced r e l i a b l y ,  5 s e c . WS  c l i c k w h i c h was  sec.  few  was  sec.  Avoidance  a 0.5  Following  that produced plate-pushing,  to determine  e v e r y 60  an  a S would push the  undertaken i n d a i l y  ex-  I f some r e s p o n s e s w e r e made, t h a t p o i n t  first  was  i f  Stimulation rarely  U s u a l l y , h o w e v e r , i t became a p p a r e n t i n t h e  sites  iso-  i n t e n s i t i e s w e r e u s e d and  recorded.  f o l l o w i n g days to see  electrode  ex-  m o t o r move-  ponse.  S and  to the  no was  presenevery  over 8 to  10  daily  week b e t w e e n m o d a l i t i e s .  S to a n o t h e r . recorded.  The  The  time from  maximum  time  The WS  - 30 -  was 16 sec. at which time the ICS was automatically terminated.  The  current used was normally just above the threshold f o r the escape response.  A score of 16 for a t r i a l resulted i n the voltage being raised  by O.lV to insure that S would make a response within 16 sec. (d) S e l f - s t i m u l a t i o n . After completion of the avoidance t r a i n i n g S were placed i n the s e l f - s t i m u l a t i o n apparatus for 30 minutes each day for several days. The number of bar presses for each 15 minute period were recorded. On some days S received no stimulation and on the remaining days r e ceived stimulation at the s e t t i n g used i n avoidance t r a i n i n g . l a t i o n and non-stimulation days were presented i n random order. were at l e a s t 3 days of stimulation. for s e l f - s t i m u l a t i o n before screening.  StimuThere  Some of the e a r l i e r S were trained This consisted of d a i l y . h a l f -  hour sessions i n the box with current a v a i l a b l e at various l e v e l s . Those S not pressing the bar were given "free" ICS i n an e f f o r t to induce (e)  responding.  Histology. At the completion of a l l testing S were anesthetized with Nembutal  and after clamping  the abdominal aorta and c u t t i n g the vena cava, physio-  l o g i c a l saline followed by 10% formalin was perfused through the heart. After soaking i n formalin overnight the brain was removed after d r i l l i n g the dental cement away from the anchoring screws and removing the electrodes.  The electrodes were checked again for i n t e g r i t y .  The brains  - 31 -  were blocked i n p a r a f f i n and cut i n 10 u sections for staining with Luxol Fast Blue and Cresyl V i o l e t (Klliver and Barrera, 1953).  The  stimulation s i t e s were taken to be the area immediately under the point of deepest penetration of the electrode.  The structure at  this point was determined by comparison with the atlas of Konig and K l i p p e l (1963) and where possible, by comparison with the nuclear structures given i n the atlas of Christ (1969).  - 32 -  RESULTS Stimulation e f f e c t s . The 30 S were implanted with a t o t a l of 81 electrodes (50 HYP, 31 MB).  Five S were eliminated from the study at the beginning due  to dislodging of the electrodes or breaking of the pin connectors. Throughout the study the number of S was reduced f o r these reasons. There were also some deaths due to r e s p i r a t o r y i n f e c t i o n and one unexplained death.  Stimulation e f f e c t s were obtained from 25 S having  a t o t a l of 67 electrode s i t e s (42 HYP, 25 MB). Of these 67 s i t e s tested for stimulation e f f e c t 22 (33%) produced forced motor movements or had high thresholds.  The e f f e c t s i n -  cluded head turning, body twisting, eye b l i n k i n g , i s o l a t e d limb movement and turning i n c i r c l e s . effect. results.  Head movements were the most frequent  The remaining 45 points were considered as giving positive In order to f a c i l i t a t e d e s c r i p t i o n these p o s i t i v e e f f e c t s  were a r b i t r a r i l y divided into 3 classes; a c t i v i t y , locomotion and running. The f i r s t class could be described as general a c t i v i t y increases, exploration, c u r i o s i t y and s n i f f i n g .  This frequently resembled  ploratory a c t i v i t y on i n i t i a l placement i n the apparatus. was r e s t r i c t e d to one area at a time.  the ex-  This a c t i v i t y  After exploration of that area,  the next one was looked at so that eventually the entire apparatus was explored.  The second pattern of behaviour, locomotion, was similar with  the exception that S explored or searched the apparatus quickly by either  - 33 -  w a l k i n g or r u n n i n g from one  p o i n t to the o t h e r .  In the l a r g e t e s t  chamber S moved a l o n g the w a l l s i n a predominant c l o c k w i s e or c l o c k w i s e d i r e c t i o n , u s u a l l y p a u s i n g a t the c o r n e r s sniff.  Other  There was  haviour  S j u s t walked or r a n i n a g e n e r a l c i r c u l a r p a t t e r n .  third  (ERB).  c l a s s of behaviour I t was  Typically  t h i s was  motionless  called  box.  e p i s o d i c running  be-  to the w i l d , f r a n t i c r u n n i n g  and  s e i z u r e , hence the d e s i g n a t i o n  ERB.  an a l l - o r - n o n e phenomenon i n t h a t the S e i t h e r  sat  or b u r s t i n t o f r a n t i c r u n n i n g when a c e r t a i n c u r r e n t t h r e s -  passed.  a l l y , was  was  very s i m i l a r  jumping seen d u r i n g an a u d i o g e n i c  h o l d was  to l o o k around or  some jumping, u s u a l l y a t the c o r n e r s of the  The  counter-  In some S t h i s  not as s h a r p .  t h r e s h o l d , e l e c t r i c a l l y or  A t c u r r e n t l e v e l s below the ERB  would r u n i n t e r m i t t e n t l y or d a r t r a p i d l y from one  behaviour-  threshold S  p o i n t to  another.  Even though these motor e f f e c t s were q u i t e s p e c t a c u l a r , the c u r r e n t producing  them was  not d i f f e r e n t  from  t h a t p r o d u c i n g other  behaviours.  Table I shows the number of e l e c t r o d e s i t e s p r o d u c i n g c l a s s e s of b e h a v i o u r . stimulation site.  I t also c l a s s i f i e s  t h a t ERB  other b e h a v i o u r s  were o b t a i n e d from  resembled  was  obtained mostly  f a s t r u n n i n g and  e x p l o s i v e r u n n i n g o b t a i n e d from have such a sharp  threshold.  the HYP.  from  the MB  The ERB  classificawhile  obtained  the from  jumping more than i t resembled  the MB.  Hypothalamic  Some S i n the l o c o m o t i o n  three  a c c o r d i n g to the  I n s p i t e of the a r b i t r a r y n a t u r e of the  tion i t i s clear  the HYP  the response  these  ERB  the  a l s o d i d not  category,  parti-  - 34 -  Table I Type and frequency of stimulation e f f e c t s in hypothalamus and midbrain.  Effect  HYP  MB  Activity  13  1  Locomotion  10  2  ERB  4  15  - 35 -  c u l a r l y those showing w a l k i n g or r u n n i n g , would a t h i g h e r c u r r e n t produce ERB.  S i m i l a r l y i n c r e a s e d s t i m u l a t i o n o f an " a c t i v i t y "  c o u l d produce " l o c o m o t i o n " . haviour cluded  levels  site  I n a l l t h r e e c a t e g o r i e s some S showed be-  i n d i c a t i v e o f an a t t e m p t to g e t o u t o f the a p p a r a t u s . jumping towards the open t o p o f the box or p u s h i n g  of the p l a s t i c door ( t h e c o r n e r o p p o s i t e  This i n -  on a c o r n e r  the h i n g e s ) .  Escape. From t h e group o f 45 p o s i t i v e s i t e s as d e t e r m i n e d above, 31 were t e s t e d i n the p l a t e - b o x  t o see i f ICS would produce  Where n e g a t i v e and p o s i t i v e s i t e s o c c u r r e d tested.  i n the same a n i m a l , b o t h were  S u c c e s s f u l p l a t e - p u s h i n g was o b t a i n e d  positive sites.  This represents  t h a t were s c r e e n e d .  plate-pushing.  from 7 (23%) o f the  10% o f the s i t e s or  257„  o f the a n i m a l s  Each S v a r i e d i n t h e number o f ICS p r e s e n t a t i o n s  required to e s t a b l i s h plate-pushing.  S u b j e c t s w i t h MB e l e c t r o d e s pushed  i t on the f i r s t t r i a l w h i l e those w i t h HYP e l e c t r o d e s took up t o 5 t r i a l s . I n a l l c a s e s the a r e a o f t h e p l a t e was t h e c e n t e r of a t t e n t i o n f o r those S t h a t l a t e r pushed i t . t r i a l s given.  S u b j e c t s a l s o v a r i e d i n t h e t o t a l number o f  T a b l e I I summarizes the b e h a v i o u r  o f the p l a t e - p u s h e r s  (as c l a s s i f i e d a b o v e ) , the e l e c t r o d e s i t e , the t h r e s h o l d f o r p l a t e pushing  and the number o f escape  trials.  Escape l a t e n c i e s were a t f i r s t q u i t e v a r i a b l e and remained way u n t i l an optimum v o l t a g e was d e t e r m i n e d .  that  Too low a v o l t a g e would  not produce p l a t e - p u s h i n g and too h i g h a v o l t a g e d i s r u p t e d performance  - 36 -  Table I I Behaviour, location,  threshold and number of t r i a l s  for escape subjects.  Effect  Activity  Locomotion  ERB  Rat number  Location of electrode  Threshold (volts)  Number of escape t r i a l s  47  HYP  0.6  235  48  HYP  0.6  20  43  HYP  0.8  325  50  HYP  0.9  145  61  HYP  1.0  30  48  MB  1.0  300  56  MB  1.10  55  - 37 -  u s u a l l y by producing gnawing or wild running. r e l a t i o n s h i p of voltage to latency for 4 s i t e s . voltage produced faster responding. of higher voltage i s c l e a r l y seen. duced by 1.10V.  Figure 4 shows the In general, increased  For S # 43 the disrupting e f f e c t For # 56 the best response was  pro-  The 1 sec. latency i s maximum that S i s p h y s i c a l l y  capable of performing.  The method used by each subject i n plate-  pushing also contributed to v a r i a t i o n i n latencies.  On some t r i a l s S  would c i r c l e the box before pressing (# 43, 61, 47), jump i n two corners before pressing (# 47), gnaw (# 43, 61), or perform a stereotyped head and neck movement ( 48 HYP ) . 47 to reduce these behaviours. at reduced frequency. teristic.  Extensive t r a i n i n g was  given to S 43 and  C i r c l i n g before pressing persisted but  The response from the MB rats was  quite charac-  At below threshold levels they sat quietly and at above  threshold levels responded  (sometimes after a short latent period) with  a d i r e c t and lightning f a s t movement.  Hypothalamic  responses were  slower and more deliberate. Another  source of v a r i a t i o n was changing thresholds. A within  session change was most conspicuous i n the case of the MB electrodes in S 48 and 56.  Subject # 48 would not respond to less than  1.40V  at the beginning of a session but by the end, would respond to 1.0V . This i s also shown by the decreased latency over t r i a l s at a given v o l tage as shown i n Figure 5. escape t r i a l s .  This pattern persisted throughout  300  Subject # 56 behaved i n an opposite manner; latency  38  Figure 4  Mean escape time versus stimulating voltage f o r subjects 43, 48, 50 and 56.  The means are based on 5 to 10  consecutive one minute  trials.  Ordinate:  mean escape time ( s e c ) ;  Abscissa:  voltage.  MEAN  ro l  OJ  -j*  oi  1  1  1  o r  ^ 1  I  ESCAPE  TIME  (SEC)  CM  ^k.  cn  01  -J  1  1  1  1  1  oo :  '  Figure 5  Escape latency as a function of time for subjects 48 and 56. listed.  The presentation of voltages i s i n the order  LATENCY  (SEC)  LATENCY  (SEC)  - 40 -  increased within a session.  I t was necessary to increase voltage  during a session or, for a given voltage, latencies progressively increased trials.  (Figure 5).  This was more obvious i n blocks of 10 or 20  For both S however there was a current l e v e l which produced  r e l i a b l e performance.  Avoidance. Five of the 7 escape points were used i n avoidance t r a i n i n g . Subjects 47 and 48 (HYP) were excluded because of r a p i d l y d e t e r i o r a t i n g performance and motor side e f f e c t s r e s p e c t i v e l y .  In spite of adequate  responding to ICS and 200 to 600 pairings with various warning s t i m u l i , a l l S f a i l e d to avoid ICS.  One S (# 43) made 12 avoidances i n 200  t r i a l s , two made 3 (# 50, 61) and two made no avoidance responses (# 48, 56).  When the t o t a l number of avoidance t r i a l s i s considered  mum avoidance rate was 3%.  the maxi-  In considering i n d i v i d u a l sessions of 20  t r i a l s , the maximum avoidance rate was 207» and this occurred only once. There was no tendency for S as a group to improve over sessions The order of WS modalities presented  (Figure 6).  to each S and the average res-  ponse time for each session (with i t s standard deviation) are presented i n Table I I I . among sessions. for  To be noted i s the v a r i a t i o n within a session and v a r i a t i o n Among sessions there i s no tendency to respond faster  any s i t e or modality with the possible exception of 56L. When res-  ponding was the f a s t e s t and with the least v a r i a b i l i t y (48C)  the escape  latency was never faster than the 1 sec. maximum that this S would per-  41  Figure 6  Mean latency (+ standard  deviation) per session f o r  a l l subjects as a function of the number of t r a i n i n g sessions.  The dotted l i n e represents  time required f o r i t to be considered  the response an avoidance.  Table III  Mean response time per session (+ standard deviation) f o r each subject and WS modality.  DAYS  S No. WS 1  43 (HYP)  48 (MB)  50 (HYP)  56 (MB) 61 (HYP)  2  3  4  5  6  7  8  9  8.73+2.54  8.98+3.43  9.78+2.46  10  L  13.18+3.02 12.00+2.88  8.29+1.16  9.94+3.33 10.49+3.03  9.66+3.54  B  9.42+3.99 10.56+3.60  9.08+3.45  9.99+3.78  9.50+5.15  9.69+4.23 10.10+2.48  8.51+1.09 10.00+3.06  C  7.72+1.44  9.08+2.15  7.88+1.80 10.38+2.49  7.67+1.36  8.29+1.85  7.56+1.34  8.62+1.77  L  6.66+0.20  8.18+0.67 10.84+1.73 11.06+3.27  9.48+2.60  9.00+1.22  9.60+1.13  7.46+0.63 10.27+2.69  B  8.50+1.06  6.91+0.58  7.88+1.04 10.31+1.50  8.74+2.25  7.90+0.83  8.39+0.91 10.17+1.11  9.02+1.02  -  C  6.70+0.11  6.53+0.25  6.60+0.16  6.55+0.17  6.54+0.11  6.53+0.15  6.52+0.12  6.52+0.16  6.56+0.13  B  11.62+1.19 10.51+1.90  6.51+0.11  7.60+1.33  9.79+1.55 10.59+1.08 10.85+2.33  9.80+4.23 11.06+1.27 10.31+0.91 10.41+1.11  9.55+2.44  8.08+1.58  -  -  L  7.77+0.74  7.64+0.63  7.67+0.66  8.61+0.65  8.72+0.72  8.28+0.75  7.81+0.45  7.75+0.54  7.52+0.62  7.95+0.81  B  7.00+0.81  6.81+0.38  8.44+2.40  8.09+2.50  8.44+2.44  9.71+3.60  8.13+2.51  7.05+0.42  -  -  L  9.47+2.11  9.33+3.77  9.06+3.20  6.79+0.39  6.62+0.15  8.29+1.69  6.78+0.37  7.68+0.89  7.57+1.25  8.04+1.05  L  9.89+4.48 11.09+2.73 10.27+2.89 10.82+3.11 12.46+2.37 11.60+3.75 12.52+3.12  9.82+3.75 11.87+3.60  -  4>  - 43 -  form without a WS. continued  Subjects with longer and more variable latencies  to perform i n this way with a s l i g h t decrement over sessions  i n some cases.  Over sessions and modalities there was a general  dency for the required voltage to increase.  ten-  Within session v a r i a b i l i t y  was generally larger for long latencies (43L) and smaller f o r short latency responses (48C).. This i n turn was r e l a t e d to the voltage and the threshold changes mentioned previously for escape.  In contrast to  most of the escape sessions, an e f f o r t was made to maintain a steady voltage.  Progressive increases i n latency within a session up to the  maximum allowed necessitated the r a i s i n g of the voltage to maintain a response thus producing  a higher mean and standard deviation.  showed faster responses within a session (43,48).  Two S  Other inconsisten-  cies i n response which also occurred for escape contributed to v a r i a t i o n here a l s o . One such v a r i a t i o n mentioned previously was the stereotyped ponse such as c i r c l i n g before responding.  res-  This also occurred here but  i t was noted that on some t r i a l s a preparatory response was made. was obvious i n the case of the S that c i r c l e d .  This  They would come to the  plate i n preparation for ICS at which time they responded without circling.  Such preparatory responses were occurring at a maximum of  50% of the time but usually l e s s .  The behaviour  of the MB subjects  was i n t e r e s t i n g i n that # 56 always stayed near the plate and # 48 always faced the wall opposite  the plate.  Both responded quickly and d i r e c t l y  but produced variable latencies at times due to a strong e f f e c t of a small change of voltage on the response time near the threshold.  - 44 -  Self-stimulation. Table IV summarizes the r e s u l t s , f o r the 5 S used i n the avoidance training. the box.  Most bar-presses occurred within 5 min. of being placed i n After S had explored the box they remained inactive  out most of the remaining when ICS was a v a i l a b l e .  time.  through-  This behaviour was generally the same  For S 43 and 50 the rate with stimulation was  s i g n i f i c a n t l y above the non-stimulation rate as determined by a MannWhitney U-test (Sokal and Rohlf, 1969)..  That the apparatus was capable  of generating high bar-press rates for ICS i s shown by the rates of up to 2800/30 min. obtained from another  electrode s i t e i n # 50.  Similar  high rates were obtained from other S which were tested before the platepushing  test.  Histology. The stimulation s i t e s for S which were tested for plate-pushing were plotted on diagrams of coronal sections from the atlas of Kbnig and K l i p p e l (1963).  Figure 7 shows the location of electrodes which  produced plate-pushing.  Figure 8a and 8b shows the HYP and MB s i t e s  r e s p e c t i v e l y which did not.  Successful escape was produced by elec-  trodes i n the MB central gray (483, 563) and i n the HYP near the f o r n i x . One s i t e was medial to the fornix i n the dorsomedial  nucleus  (505) and  the rest were located l a t e r a l to the fornix i n the region of the medial forebrain bundle (MFB) i n the l a t e r a l hypothalamus (475, 614) and bordering on the f i e l d s of F o r e l and zona incerta (435, 485). Figure 8 shows  - 45 -  Table  IV  Average bar pressing rate with and without ICS at the voltage indicated.  Rat no.  Electrode site  Average rate/30 min  Average rate/30 min  No stimulation  Stimulation  Voltage  *  43  HYP  5  38  48  MB  8  12  50  HYP  24  54  56  MB  14  19  1.50  61  HYP  16  15  1.20  1.40  *  S i g n i f i c a n t l y above no stimulation rate ( p^O.OS, 1-tailed Mann-Whitney U-test ).  1.20  1.0  46  Figure 7  L o c a t i o n of e l e c t r o d e s producing pushing. and  Sites are i d e n t i f i e d  escape by p l a t e -  by the s u b j e c t  the p i n number o f the e l e c t r o d e .  Solid  number  circles  s i g n i f y a l o c o m o t i o n s t i m u l a t i o n e f f e c t and s o l i d squares r e p r e s e n t coordinate  an ERB e f f e c t .  The a n t e r o - p o s t e r i o r  from these s e c t i o n s from the a t l a s o f  K o n i g and K l i p p e l (1963) a r e g i v e n of each s e c t i o n .  i n the upper  left  47  Figure 8  Location of electrodes f a i l i n g to produce escape by plate-pushing: (a)  Hypothalamus  (b)  Midbrain  Same designation as for Figure 7 with the addition of an open c i r c l e to represent forced motor movements. Sites 472 and 452 are open c i r c l e s cerebral aqueduct.  located i n the  595  465  455  - 48 -  that some of the electrodes having extrapyramidal or no e f f e c t were located outside the brain, i n the cerebral aqueduct structures.  or i n subthalamic  However, many of the sites producing locomotion or ERB  were located i n structures apparently i d e n t i c a l to those producing similar e f f e c t s and escape as shown i n Figure 7.  - 49 DISCUSSION The main stimulation e f f e c t obtained from the HYP and MB could be c a l l e d simply motor a c t i v i t y . haviour were distinguished: wild-running.  More s p e c i f i c a l l y , three classes of beforced motor movements, locomotion, and  Forced motor movements are of i n t e r e s t mainly to those  studying the central control of motor systems (Koella, 1969) but they occur frequently as an a d d i t i o n a l behaviour or a " s i d e - e f f e c t " of s t i mulation.  Most studies report these effects as such.  that these effects can i n t e r f e r e with the performance (Mogenson, 1962).  being evaluated  I t was observed here both the motor effects which  did not e l i c i t subsequent  plate-pushing and those which were  on a plate-pushing behaviour. the MB was  I t has been noted  superimposed  Wild running, frequently obtained from  labelled episodic running behaviour (ERB) due to i t s resemblance  to part of an audiogenic seizure (Wada and Ikeda, 1966). c a l l e d rapid intermittent locomotion (Woodworth, 1971).  I t has also been I t i s usually  d i f f i c u l t to control and so i s included with the motor e f f e c t s as a reason for screening the S from an experiment  (Cox, 1967).  There are cases, par-  t i c u l a r l y i n the HYP where a reduced current produces less than wild running.  Such S are l i k e l y to succeed i n a shuttle-box or runway task.  The third class of behaviour i d e n t i f i e d i n this study was which varied from slow walking to less than f r a n t i c running.  locomotion  The speed  at which this i s done i s proportional to the current i n t e n s i t y .  Such be-  haviour i s i d e a l l y suited for shuttlebox and runway tasks since the f o r ward locomotion would eventually get the animal to the " o f f " side.  In  - 50 -  i t s less intense form i t resembles exploratory a c t i v i t y .  In l i n e with  the e t h o l o g i c a l approach to behaviour i t can be noted that the tory a c t i v i t y seen here and elsewhere (Roberts, 1970)  1969;  i s a s p e c i e s - s p e c i f i c behaviour i n the r a t and  along the wall of the test box thigmotaxic  explora-  Valenstein et a l , that the running  seen here resembles the s p e c i e s - s p e c i f i c  response (Bafnett, 1963).  Roberts (1969, 1970)  and  Valenstein  et a l (1970) note that exploratory locomotion i s seen i n the absence of environmental s t i m u l i with which S can i n t e r a c t or when a goal directed consummatory response (such as eating, drinking or gnawing) has not yet been established.  I t seems then, that ICS induced exploration i s a be-  haviour waiting to happen, given appropriate environmental circumstances. In the screening procedure used here such conditions were a v a i l able to a c e r t a i n extent.  Some S behaved as i f they were t r y i n g to get  out of the box either by jumping i n the corners or t r y i n g to widen the crack i n the door.  The f r a n t i c searching, darting, running movements  of some S could also be interpreted as f l i g h t , perhaps more appropriately than the other  since this i s the kind of behaviour that would benefit the  animal i n a r e a l l i f e - t h r e a t e n i n g s i t u a t i o n . more appropriate i t was  The plate-box provides  a  environment for the S to display f l i g h t behaviour and  found that some rats would push the plate to terminate ICS.  The  rat's behaviour i s , therefore, s i m i l a r to that described as f l i g h t i n cats (Roberts,  1958a; Skultety, 1963)  cats (Nakao, 1958;  and produces plate-pushing  Wada and Matsuda, 1970;  Wada et a l , 1970).  t i v e l y the two classes of f l i g h t distinguished, locomotion and comparable with Yasukochi's "fear" and  as i n  QualitaERB,  are  "yearning" and Brown et a l (1969a)  - 51 -  type "b" and type "a" f l i g h t responses r e s p e c t i v e l y .  The d e s c r i p t i o n  of Brown et a l i n cats corresponds quite c l o s e l y with the behaviour observed here; i . e . quiet, deliberate f l i g h t and rapid, agitated, aroused f l i g h t .  Analogous with f l i g h t Flynn et a l (1970) found a  "quiet b i t i n g attack" and "affective attack" i n cats.  Even though  these behaviours are q u a l i t a t i v e l y d i f f e r e n t , t h e i r outcome i n terms of either f l i g h t or attack i s the same.  Once again i t must be stressed  that appropriate environmental objects must be present for these behaviours to be shown. A further observation, made i n cats by Wada and Matsuda (1970), Wada et a l (1970) and i n rats i n the present study, was that not a l l points showing manifestations of searching or f l i g h t would produce in the plate-box.  escape  Only 50% of the cats and 25% of the rats would escape.  This i s not unreasonable i n view of the f a c t that most of the rats' behaviour i s subject to large amounts of i n t e r p r e t a t i o n and that the exploratory behaviour commonly seen can be prerequisite to any number of responses i f a goal object i s present (Valenstein et a l , 1970). ation can presumably  The plate-box s i t u -  s e l e c t only those behaviours related to f l i g h t as  defined by attempts of the S to remove themselves from the apparatus. The a l t e r n a t i v e , which might be c a l l e d non-specific s e l e c t i o n of a p l a t e pushing response, i s u n l i k e l y i n view of the i n a b i l i t y of the escape response even after extensive t r a i n i n g to transfer to another electrode i n the same animal; and the observation that only one of a pair of c l o s e l y spaced electrodes produced escape i n spite of the otherwise i d e n t i c a l stimulation effects for both.  In this l a t t e r s i t u a t i o n i t i s p a r t i c u l a r l y  - 52 -  o b v i o u s t h a t the p l a t e - p u s h i n g t e s t i s more d i s c r i m i n a t i v e than a s h u t t l e - b o x t e s t s i n c e b o t h b e h a v i o u r s ( f o r w a r d l o c o m o t i o n ) would g i v e good performance  i n the s h u t t l e - b o x or i n a runway.  Even though r a t s would escape from HYP and MB  ICS by p l a t e -  p u s h i n g , none o f these same r a t s would a v o i d i t by r e s p o n d i n g d u r i n g a s i g n a l w h i c h p r e d i c t e d the o c c u r r e n c e of ICS.  E x c e p t f o r the r e -  p o r t by Mogenson (1962), these r e s u l t s a r e i n agreement w i t h o t h e r a t t e m p t s to produce a v o i d a n c e of ICS i n the r a t ( S t e i n , 1965; 1967; Bower and M i l l e r , 1958; 1971).  Cox,  Johnson and Levy, 1969; W o l f l e e t a l ,  They a r e a l s o i n agreement w i t h R o b e r t s ' (1958a) and Wada and  Matsuda's (1970) r e s u l t s w i t h HYP  ICS i n c a t s .  I n g e n e r a l , the r e s u l t  o f no a v o i d a n c e i s found w i t h a l l  types of a p p a r a t u s .  F a i l u r e to produce a v o i d a n c e of ICS i s not a g e n e r a l p r o p e r t y o f a l l s i t e s i n the b r a i n .  A v o i d a n c e has been o b t a i n e d by Nakao (1958),  Cohen e t a l (1957), Brown and Cohen (1959), Romaniuk (1964) and R o b e r t s (1958a) i n a number of s i t u a t i o n s and u s i n g s t i m u l a t i o n o f a r e a s to those f a i l i n g to produce a v o i d a n c e .  similar  More i n t e r e s t i n g a r e the cases  where a v o i d a n c e has been o b t a i n e d from the MB but not the HYP  (Wada e t a l ,  1970) or where a v o i d a n c e o c c u r s i n some a n i m a l s and not o t h e r s i n the same e x p e r i m e n t  (Stokman and Glusman, 1970; W o l f l e e t a l , 1971; R o b e r t s ,  1958a; F o n b e r g ,  1967).  I n some cases t h i s can be a t t r i b u t e d to d i f f e r e n c e s  i n s t i m u l a t i o n e f f e c t or e l e c t r o d e s i t e .  W o l f l e e t a l (1971) found  dif-  f e r e n c e s i n a v o i d a n c e between s i t e s i n c e n t r a l g r a y and s i t e s i n a d j a c e n t tegmentum.  Wada e t a l ( 1 9 7 0 ) , however, w i t h a l l e l e c t r o d e s i n c e n t r a l  - 53 -  gray found that four out of s i x cats avoided WS,  and Stokman and  Glusman (1970) with a l l electrodes i n HYP found that one of their four cats would avoid.  Current i n t e n s i t y would seem to be a factor  but most studies used threshold l e v e l s .  In a l l these studies and  the one reported here there i s no apparent factor which might account for the differences observed. Even though there was no tendency toward avoidance i n this experiment there was  an increase i n preparatory responses.  been noted i n other studies as w e l l .  This has  That the S can form an a s s o c i -  ation between ICS and neutral stimuli i s shown i n studies where succ e s s f u l passive avoidance  (Cox, 1967) and conditioned suppression  (Wolfle et a l , 1971) have been obtained.  Wolfle et a l also used a  one-way active avoidance task and found a greater incidence of avoidance than i n the two-way s i t u a t i o n .  These techniques have been used  extensively to study the motivational properties of footshock.  In  several studies ICS has been compared with footshock. Avoidance of footshock has been used as a control i n some studies to insure that S are capable of responding.  Nakao (1958) pretrained his  cats with footshock and subsequently obtained avoidance of ICS.  Cox  (1967) comparing the two i n rats found l i t t l e transfer of t r a i n i n g to the ICS task.  Romaniuk (1964) found that the course of a c q u i s i t i o n of  an avoidance response was  the same for footshock as i t was for ICS.  comparison of footshock with ICS under contingent and  non-contingent  associations with the WS showed that the properties of ICS were quite d i f f e r e n t from footshock (Stokman and Glusman, 1970).  A  - 54 -  Just as the natural model for ICS induced eating i s the eating done by a food deprived  animal so the model for ICS induced f l i g h t i s  the behaviour induced by peripheral e l e c t r i c a l shock.  By  observing  that S do not avoid flight-producing ICS but do avoid footshock one might conclude that ICS does not induce a c e n t r a l state comparable with that produced by footshock.  This conclusion should not be made  without taking into consideration the fundamental differences between the two.  For example, footshock can disrupt performance by e l i c i t i n g  competing responses such as f r e e z i n g . as any c e n t r a l state of f e a r . safe place i f an opportunity pain may  or may  Here pain i s involved as well  The animal may i s provided  not be involved.  freeze or may  (Bolles, 1970).  run to a  With ICS  Delgado et a l (1954, 1956)  obtained  avoidance from structures involved i n the transmission of pain. ever, ICS i n the HYP (Olds, 1962)  How-  i s known to produce strongly rewarding e f f e c t s  and a hypothesis put forward by Roberts (1958a,b) seemed  to account for f a i l u r e to avoid on the basis of rewarding onset of  ICS.  In the present experiment s e l f - s t i m u l a t i o n rates were low for a l l S.  Rates without ICS are comparable to Olds and Olds (1963) rates, but  the rates with ICS are not even as high as Routtenberg's (1970) or Stein's (1965) rates for non-reward.  The c r i t e r i o n of s e l f - s t i m u l a t i o n given by  each author appears to be quite a r b i t r a r y .  Since prior stimulation ex-  perience might have produced a lower rate i n the present experiment the c r i t e r i o n of s t a t i s t i c a l s i g n i f i c a n c e was stimulation was  obtained  used.  By this method s e l f -  from two out of three animals with HYP  or two out of f i v e t o t a l electrodes.  electrodes  Although bar-press rate i s limited  - 55 -  as an indicator of reward e f f e c t (Valenstein, 1964)  i t has been used  i n a number of studies which tend to support Roberts' hypothesis. Bower and M i l l e r study stimulation.  (1958) i n r a t s used s i t e s known to produce s e l f -  In a l l experiments using the HYP  expect electrodes to give rewarding e f f e c t s . reports of s e l f - s t i m u l a t i o n from the MB Cooper and Taylor, 1967) shuttle-box escape was  The  i t i s not unreasonable to More s u r p r i s i n g are the  (Crow, 1972;  Mayer et a l , 1971;  and i n p a r t i c u l a r from the c e n t r a l gray where  obtained i n the same r a t (Wolfle et a l , 1971).  Signs of pain and fear often accompany the e f f e c t and i t takes a longer period of time for i t to develop.  Sometimes i t does not develop at a l l  and sometimes this i s i n an animal that w i l l not avoid.  There are also  some S which w i l l both avoid and s e l f - s t i m u l a t e . A l l of Brown and Cohen's (1959) cats made approach and avoidance responses at the same site.  The majority of f l i g h t points overlap with reward points but  there are enough non-overlapping  points i n the l i t e r a t u r e and p a r t i c u -  l a r l y i n the present experiment to suggest that the Roberts i s i n s u f f i c i e n t to explain a l l the data.  hypothesis  That f l i g h t and reward points  have separate mechanisms but overlapping structures i s suggested by recent demonstrations of d i f f e r i n g thresholds for reward and motivational behaviours  (Olds, A l l a n and Briese, 1971;  The HYP  B a l l , 1970;  Huston, 1971).  and MB are f u n c t i o n a l l y equivalent with regard to escape  and avoidance behaviour although a higher proportion of ERB was from MB.  obtained  Hunsperger (1956) considered the zone giving a f f e c t i v e reactions  to be continuous  from the hypothalamus to the midbrain.  He also considers  - 56 -  the HYP and MB areas as independent  sources of behaviour since the  stimulation effects of a MB s i t e are not affected by lesions r o s t r a l to i t .  The wide d i s t r i b u t i o n of s i t e s e l i c i t i n g escape i n the present  study would support the concept of an extensive system governing this type of behaviour.  Sites y i e l d i n g escape were found i n both the l a t e r a l  and medial d i v i s i o n s of the middle to posterior area of the HYP.  There  were no electrodes i n the anterior HYP or i n the posterior nucleus. These are the areas that have been used i n cats by Nakao (1958) and Roberts  (1958a) r e s p e c t i v e l y .  The posterior nucleus of the HYP i s par-  t i c u l a r l y i n t e r e s t i n g since i t gradually merges with the central gray area of the MB.  In spite of claims of homogeneity of neural systems,  there have been very few electrodes placed i n this t r a n s i t i o n zone. The l a t e r a l and dorsal boundaries of the HYP are not d i s t i n c t anatomic a l l y and the l a t e r a l hypothalamic  area merges with the zona incerta  and f i e l d s of Forel (Nauta and Haymaker, 1969), where extrapyramidal motor effects are obtained.  The main fiber system through the HYP i s  the medial forebrain bundle which has been associated with reward (Valenstein, 1966) while the corresponding system i n the central gray area i s the dorsal longitudinal fasciculus which has been associated with punishment (Olds and Olds, 1963).  The MB area i s also associated  with the termination of pain pathways from the spinal cord 1966).  (Mehler,  This along with reports of pain from MB stimulation i n man  (Nashold et a l , 1969) and pain and f e a r - l i k e a c t i v i t y i n animals make s e l f - s t i m u l a t i o n an u n l i k e l y combination with these i n the MB  yet the  bar-press rates by rats indicate that they are indeed combined.  - 57 -  The  involvement of pain i n the MB  but not the HYP  seems to be a funda-  mental difference between the two areas but the method of for ICS cannot d i s t i n g u i s h between the two. S w i l l terminate (and quickly) both HYP  Nevertheless,  and MB  bar-pressing the fact that  ICS i n this experiment  and i n others suggests that the fundamental nature of ICS i s aversive. An a l t e r n a t i v e explanation i s that ICS i s not aversive  (except at higher  i n t e n s i t i e s ) and i s only an e l i c i t e d motor behaviour which requires that the act be performed i n order  to be rewarding (Roberts,  with this i s the speculation that plate-pushing  1970).  be considered  of stimulus bound consummatory behaviour i n the same way behaviour has been considered  (Valenstein et a l , 1970;  In l i n e as a type  that feeding  Valenstein, 1969).  Valenstein's group has presented evidence showing important differences between natural and stimulus bound behaviours. apart from any reward value of ICS, i s rewarding.  One  observation i s that  the performance of the e l i c i t e d act  This, and some a d d i t i o n a l work (Valenstein, 1971)  which  showed that the response induced by ICS i s r e s i s t a n t to change after being established, could explain the f a i l u r e of S to avoid i n this periment.  Under the condition of the present  ex-  experiment, escape respon-  ding would be maintained by the rewarding consequence of performing the plate-pushing  response i n the presence of ICS.  Implied  i s that the  association of the WS with the response would be less rewarding. responding would also be maintained due been well established by p r e t r a i n i n g . have been formed between WS and  ICS,  to the f a c t that the response has Even though an association  ICS.  may  the S has been trained to respond  i n a fixed pattern using the cue properties of  Escape  (Mogenson and Morrison,  1962)  - 58 -  Although Valenstein's group has accumulated evidence  incom-  patible with the view that ICS e l i c i t s a c e n t r a l motivational state i d e n t i c a l with that produced by natural s t i m u l i , i t i s possible to gain access to the neural substrate underlying several s p e c i e s - t y p i c a l behaviours.  That they can be produced and directed towards appropriate  goals on an i n t e r a c t i v e basis with the environment, should be enough of a s i m i l a r i t y , given suitable means of q u a n t i f i c a t i o n , to further our understanding  of  behaviour.  - 59 -  REFERENCES Abrahams, V. C , S. M. H i l t o n and A. Zbrozyna. 1960. A c t i v e muscle v a s o d i l a t a t i o n produced by s t i m u l a t i o n o f t h e b r a i n stem: i t s s i g n i f i c a n c e i n the defense r e a c t i o n . J . P h y s i o l . (London) 154: 491-513. A k e r t , K. 1961. D i e n c e p h a l o n , pp. 288-310. I n " E l e c t r i c a l S t i m u l a t i o n of t h e B r a i n . " D. E. Sheer ( e d . ) . U n i v e r s i t y o f Texas P r e s s , Austin. Arnold,  M. B. 1950. An e x c i t a t o r y t h e o r y o f e m o t i o n , pp. 11-33. T_n_ " F e e l i n g s and E m o t i o n s . " M. L. Reymert ( e d . ) . M c G r a w - H i l l , New Y o r k .  Arnold,  M. B. 1960. "Emotion and P e r s o n a l i t y . " V o l . 2_. Columbia U n i v e r s i t y P r e s s , New Y o r k .  B a l i n s k a , H., A. Romaniuk and W. Wyrwicka. 1964. Impairment o f c o n d i t i o n e d d e f e n s i v e r e a c t i o n s f o l l o w i n g l e s i o n s o f the l a t e r a l hypothalamus i n r a b b i t s . A c t a B i o l . Exper. (Warsaw) 24: 89-97. B a l l , G. G. 1970. H y p o t h a l a m i c s e l f - s t i m u l a t i o n and f e e d i n g : time f u n c t i o n s . P h y s i o l . Behav. 5_: 1343-1346.  different  B a r d , P. 1928. A d i e n c e p h a l i c mechanism f o r t h e e x p r e s s i o n o f rage w i t h s p e c i f i c r e f e r e n c e t o the s y m p a t h e t i c nervous system. Amer. J . P h y s i o l . 84: 490-515. Barnett, Bindra,  S. A. 1963. "The R a t . "  Aldine,  Chicago.  D. 1969. A u n i f i e d i n t e r p r e t a t i o n o f emotion and m o t i v a t i o n . A n n a l s New York Acad. S c i . 159: 1071-1083.  B i n d r a , D. 1970. Emotion and b e h a v i o r t h e o r y : c u r r e n t r e s e a r c h i n h i s t o r i c a l p e r s p e c t i v e , pp. 3-20. I n " P h y s i o l o g i c a l C o r r e l a t e s o f E m o t i o n . " P. B l a c k ( e d . ) . Academic P r e s s , New York. B o l l e s , R. C. 1970. S p e c i e s - s p e c i f i c d e f e n s e r e a c t i o n s ning. P s y c h o l . Rev. 77: 32-48.  and a v o i d a n c e  lear-  Bower, G. H. 1959. Response l a t e n c y as a f u n c t i o n o f b r a i n s t i m u l a t i o n variables. J . Comp. P h y s i o l . P s y c h o l . 52: 533-535. Bower, G. H. and N. E. M i l l e r . 1958. Rewarding and p u n i s h i n g e f f e c t s from s t i m u l a t i n g the same p l a c e i n the r a t ' s b r a i n . J . Comp. P h y s i o l . P s y c h o l . 51: 669-674. Brady, J . V. 1960. E m o t i o n a l b e h a v i o r , pp. 1529-1552. I n "Handbook o f P h y s i o l o g y , S e c t . 1, N e u r o p h y s i o l o g y , " V o l . 3_. J . F i e l d ( e d . ) . A m e r i c a n P h y s i o l o g i c a l S o c i e t y , Washington, D.C.  - 60  -  Brown, G. W. and B. D. Cohen. 1959. A v o i d a n c e and approach l e a r n i n g m o t i v a t e d by s t i m u l a t i o n of i d e n t i c a l h y p o t h a l a m i c l o c i . Amer. J . P h y s i o l . 197: 153-157. Brown, J . L. 1969. N e u r o - e t h o l o g i c a l approaches to the s t u d y of e m o t i o n a l b e h a v i o r : s t e r e o t y p y and v a r i a b i l i t y . Ann. New York Acad. S c i . 159: 1084-1095. Brown, J . L. , R. W. Hunsperger and H. E. R o s v o l d . 1969a. Defence, a t t a c k and f l i g h t e l i c i t e d by e l e c t r i c a l s t i m u l a t i o n of the hypothalamus of the c a t . Exp. B r a i n Res. 8: 113-129. Brown, J . L., R. W. Hunsperger and H. E. R o s v o l d . 1969b. I n t e r a c t i o n of d e f e n c e and f l i g h t r e a c t i o n s produced by s i m u l t a n e o u s s t i m u l a t i o n a t two p o i n t s i n the hypothalamus of the c a t . Exp. B r a i n Res. 8_: 130-149. Cannon, W. B. 1927. The James-Lange t h e o r y of emotions: a c r i t i c a l examin a t i o n and an a l t e r n a t i v e t h e o r y . Amer. J . P s y c h o l . 39: 106-124. Cannon, W. B. 1931. A g a i n the James-Lange and e m o t i o n . P s y c h o l . Rev. 38: 281-295.  the  thalamic theories  of  Cohen, B. D., G. W. Brown and M. L. Brown. 1957. A v o i d a n c e l e a r n i n g m o t i v a t e d by h y p o t h a l a m i c s t i m u l a t i o n . J . E x p e r . P s y c h o l . J53: 228-233. Cooper, R. M. and L. H. T a y l o r . grey: s e l f - s t i m u l a t i o n . Cox,  1967. Thalamic r e t i c u l a r system and S c i e n c e 156: 102-103.  V. C. 1967. A v o i d a n c e c o n d i t i o n i n g w i t h c e n t r a l and s i v e s t i m u l a t i o n . Can. J . P s y c h o l . _21: 425-435.  peripheral  Crow, T. J . 1972. A map of the r a t mesencephalon f o r e l e c t r i c a l s t i m u l a t i o n . B r a i n Res. 36^: 265-273.  central aver-  self-  C h r i s t , J . F. 1969. D e r i v a t i o n and b o u n d a r i e s o f the hypothalamus, w i t h a t l a s of h y p o t h a l a m i c g r i s e a , pp. 13-60. In "The Hypothalamus." W. Haymaker, E. Anderson and W. J . H. Nauta ( e d s . ) . C h a r l e s C. Thomas, Springfield. D e l g a d o , J . M. R., W. W. R o b e r t s , and N. E. M i l l e r . 1954. L e a r n i n g m o t i v a t e d by e l e c t r i c a l s t i m u l a t i o n of the b r a i n . Amer. J . P h y s i o l . 179: 587-593. Delgado, J . M. R., H. E. R o s v o l d and E. Looney. 1956. E v o k i n g c o n d i t i o n e d f e a r by e l e c t r i c a l s t i m u l a t i o n of s u b c o r t i c a l s t r u c t u r e s i n the monkey b r a i n . J . Comp. P h y s i o l . P s y c h o l . 49: 373-380. Doty, R. W. Ann.  1969. E l e c t r i c a l s t i m u l a t i o n of the b r a i n i n b e h a v i o r a l Rev. P s y c h o l . 20: 289-320.  context.  - 61 -  F e h r , F. S. and J . A. S t e r n . 1970. P e r i p h e r a l p h y s i o l o g i c a l v a r i a b l e s and emotion: the James-Lange t h e o r y r e v i s i t e d . Psychol. B u l l . 74: 411-424. Fernandez De M o l i n a , A. and R. W. Hunsperger. 1959. C e n t r a l r e p r e s e n t a t i o n of a f f e c t i v e r e a c t i o n s i n f o r e b r a i n and b r a i n s t e m . E l e c t r i c a l s t i m u l a t i o n of amygdala, s t r i a t e r m i n a l i s , and a d j a c e n t s t r u c t u r e s . J . P h y s i o l . (London) 145: 251-265. Fernandez De M o l i n a , A. and R. W. Hunsperger. 1962. O r g a n i z a t i o n o f the s u b c o r t i c a l system g o v e r n i n g defence and f l i g h t r e a c t i o n s i n the cat. J . P h y s i o l . . (London) 160: 200-213. F l y n n , J . P., H. Vanegas, W. F o o t e and S. Edwards. 1970. N e u r a l mechanisms i n v o l v e d i n a c a t ' s a t t a c k on a r a t , pp. 135-173. In "The N e u r a l C o n t r o l o f B e h a v i o r . " R. E. Whalen, R. F. Thompson, M. Verzeano and N. M. Weinberger (eds.).Academic P r e s s , New York. Fonberg, E. 1967. The m o t i v a t i o n a l r o l e o f the hypothalamus h a v i o r . A c t a B i o l . Exper. (Warsaw) 27: 303-318.  i n a n i m a l be-  Glusman, M. and L. R o i z i n . 1960. R o l e o f the hypothalamus i n the o r g a n i z a t i o n of a g o n i s t i c b e h a v i o r i n the c a t . T r a n s . Amer. N e u r o l . A s s . 85: 177-181. G o l d s t e i n , M. L. 1968. P h y s i o l o g i c a l t h e o r i e s of emotion: a c r i t i c a l h i s t o r i c a l r e v i e w from the s t a n d p o i n t of b e h a v i o r t h e o r y . Psychol. B u l l . 69: 23-40. Grossman, S. P. 1967. "Textbook o f P h y s i o l o g i c a l P s y c h o l o g y . " W i l e y and Sons, New York. Hammond, L. J . 1970. C o n d i t i o n e d e m o t i o n a l s t a t e s , pp. 245-259. I n " P h y s i o l o g i c a l C o r r e l a t e s o f Emotion." P. B l a c k (ed.).Academic P r e s s , New York. Heath, R. G. and W. A. M i c k l e . 1960. E v a l u a t i o n o f seven y e a r s ' e x p e r i ence w i t h depth e l e c t r o d e s t u d i e s i n human p a t i e n t s , pp. 214-242. In " E l e c t r i c a l S t u d i e s on the U n a n e s t h e t i z e d B r a i n . " E. R. Ramey and D. S. O'Doherty ( e d s . ) . Hoeber, New York. Hess, W. R. 1954. "Diencephalon: Autonomic Grune and S t r a t t o n , New York.  and E x t r a p y r a m i d a l F u n c t i o n s . "  Hunsperger, R. W. 1956. A f f e k t r e a k t i o n e n auf e l e k t r i s c h e r e i z u n g im hirnstamm der k a t z e . H e l v . P h y s i o l . A c t a 14: 70-92. Hunsperger, R. W. 1963. Comportements a f f e c t i f s provoques par l a stimul a t i o n e l e c t r i q u e du t r o n c c e r e b r a l e t du c e r v e a u ante"rieur. J . P h y s i o l . ( P a r i s ) 55: 45-98.  - 62 -  Huston, J . P. 1971. R e l a t i o n s h i p between m o t i v a t i n g and rewarding s t i m u l a t i o n o f the l a t e r a l hypothalamus. P h y s i o l . Behav. 6_: 711-716. Johnson, R. N. and R. S. Levy. 1969. Escape and avoidance l e a r n i n g f o r d i s c o n t i n u o u s ICS as a f u n c t i o n o f i n t e r t r i a l i n t e r v a l . Psychon. S c i . 14: 106-108. K l l i v e r , H. and P. C. Bucy. 1939. P r e l i m i n a r y a n a l y s i s o f f u n c t i o n s of the temporal lobes i n monkeys. A r c h . N e u r o l . P s y c h i a t . ( C h i c a g o ) , 42: 979-1000. K l i i v e r , H. and E. B a r r e r a . 1953. A method f o r the combined s t a i n i n g o f c e l l s and f i b e r s i n the nervous system. J . N e u r o p a t h o l . Exper. N e u r o l . 12: 400-403. Konig,  J . F. R. and R. A. K l i p p e l . Wilkins, Baltimore.  1963. "The Rat B r a i n . " W i l l i a m s and  K o e l l a , W. P. 1969. C o n t r o l o f s k e l e t a l motor a c t i v i t y , w i t h emphasis on the r o l e o f d i e n c e p h a l i c mechanisms, pp. 645-658. I n "The Hypothalamus." W. Haymaker, E . Anderson, and W. J . H. Nauta ( e d s . ) . C h a r l e s C. Thomas, S p r i n g f i e l d . MacLean, P. D. 1949. Psychosomatic d i s e a s e and t h e " v i s c e r a l b r a i n " . Psychosom. Med. _U: 338-353. MacLean, P. D. 1955. The l i m b i c system ( " v i s c e r a l b r a i n " ) i n r e l a t i o n to c e n t r a l g r a y and r e t i c u l u m o f the b r a i n s t e m . Psychosom. Med. 17: 355-366. M a r g u l e s , D. L. and J . O l d s . 1962. I d e n t i c a l " f e e d i n g " and " r e w a r d i n g " systems i n the l a t e r a l hypothalamus of r a t s . S c i e n c e 135: 374-375. Masserman, J . H. 1941. I s the hypothalamus a c e n t e r o f emotion? Med. 3: 3-25. Masserman, J . H. 1943. "Behavior Chicago.  Psychosom.  and N e u r o s i s . " U n i v e r s i t y of Chicago  Press,  Mayer, D. J . , T. L. W o l f l e , H. A k i l , B. Carder and J . C. L i e b e s k i n d . 1971. A n a l g e s i a from e l e c t r i c a l s t i m u l a t i o n i n the b r a i n s t e m of the r a t . S c i e n c e 174: 1351-1354. Mehler, W. R. 1966. Some o b s e r v a t i o n s on secondary a s c e n d i n g a f f e r e n t systems i n the c e n t r a l nervous system, pp. 11-32. Ln " P a i n . " R. S. K n i g h t o n and P. B. Dumke ( e d s . ) . L i t t l e , Brown, Boston.  - 63 -  M i l n e r , P. M. 1970. " P h y s i o l o g i c a l P s y c h o l o g y . " Winston, New York.  H o l t , R i n e h a r t and  Mogenson, G. J . 1962. Avoidance l e a r n i n g t o a v e r s i v e b r a i n s t i m u l a t i o n . P s y c h o l . Rep. 10: 558. Mogenson, G. J . and M. J . M o r r i s o n . 1962. Avoidance r e s p o n s e s to "reward" s t i m u l a t i o n o f the b r a i n . J . Comp. P h y s i o l . P s y c h o l . 55_: 691-694. Nakao, H. 1958. E m o t i o n a l Amer. J . P h y s i o l .  behavior  produced by h y p o t h a l a m i c s t i m u l a t i o n .  194: 411-418.  Nakao, H., M. Yoshida and T. S a s a k i . 1968. M i d b r a i n c e n t r a l gray and s w i t c h - o f f b e h a v i o r i n c a t s . Jap. J . P h y s i o l . 18_: 462-470. N a s h o l d , B. S., J r . , W. P. W i l s o n and D. G. S l a u g h t e r . 1969. S e n s a t i o n s evoked by s t i m u l a t i o n i n the m i d b r a i n o f man. J . Neurosurg. 30:  14-24.  Nauta, W. J . H. and W. Haymaker. 1969. Hypothalamic n u c l e i and f i b e r c o n n e c t i o n s , pp. 136-209. In_ "The Hypo thalamus." W. Haymaker, E. Anderson, and W. J . H. Nauta ( e d s . ) . C h a r l e s C. Thomas, Springfield. Olds,  J . 1962. Hypothalamic s u b s t r a t e s of reward.  Olds,  J . , W. S. A l l a n and E. B r i e s e . 1971. D i f f e r e n t i a t i o n o f h y p o t h a l a m i c d r i v e and reward c e n t e r s . Amer. J . P h y s i o l . 221: 368-375.  Olds,  J . and P. M i l n e r . 1954. P o s i t i v e r e i n f o r c e m e n t produced by e l e c t r i c a l s t i m u l a t i o n o f s e p t a l a r e a and o t h e r r e g i o n s o f r a t b r a i n . J . Comp. P h y s i o l . P s y c h o l . 47: 419-427.  554-604.  P h y s i o l . Rev. 42:  O l d s , M. E . and J . O l d s . 1963. Approach-avoidance a n a l y s i s o f r a t d i e n c e p h a lon. J . Comp. N e u r o l . 120: 259-295. Papez, J . W. 1937. A proposed mechanism o f emotion. (Chicago) 38: 725-743.  Arch.  Neurol.  Psychiat.  Panksepp, J . 1971. A g g r e s s i o n e l i c i t e d by e l e c t r i c a l s t i m u l a t i o n o f the hypothalamus i n a l b i n o r a t s . P h y s i o l . Behav. 6_: 321-329. Panksepp, J . and J . T r o w i l l . 1969. E l e c t r i c a l l y induced a f f e c t i v e a t t a c k from the hypothalamus o f the a l b i n o r a t . Psychonom. S c i . 16:  118-119.  - 64 -  Renfrew, J . W. 1969. The i n t e n s i t y f u n c t i o n and r e i n f o r c i n g p r o p e r t i e s of b r a i n s t i m u l a t i o n t h a t e l i c i t s a t t a c k . P h y s i o l . Behav. 4: 509-515. R o b e r t s , W. W. 1958a. R a p i d escape l e a r n i n g w i t h o u t a v o i d a n c e l e a r n i n g m o t i v a t e d by h y p o t h a l a m i c s t i m u l a t i o n i n c a t s . J . Comp. P h y s i o l . P s y c h o l . 51: 391-399. R o b e r t s , W. W. 1958b. Both r e w a r d i n g and p u n i s h i n g e f f e c t s from s t i m u l a t i o n o f p o s t e r i o r hypothalamus o f c a t w i t h same e l e c t r o d e a t same intensity. J . Comp. P h y s i o l . P s y c h o l . 5_1: 400-407. R o b e r t s , W. W. 1969. A r e h y p o t h a l a m i c m o t i v a t i o n a l mechanisms f u n c t i o n a l l y and a n a t o m i c a l l y s p e c i f i c ? B r a i n Behav. E v o l . 2r. 317-342. R o b e r t s , W. W. 1970. H y p o t h a l a m i c mechanisms f o r m o t i v a t i o n a l and s p e c i e s t y p i c a l b e h a v i o r , pp. 175-206. Tn "The N e u r a l C o n t r o l o f B e h a v i o r . R. E. Whalen, R. F. Thompson, M. Verzeano and N. M. Weinberger (eds Academic P r e s s , New York. R o b e r t s , W. W., M. L. S t e i n b e r g and L. W. Means. 1967. H y p o t h a l a m i c mechanisms f o r s e x u a l , a g g r e s s i v e and o t h e r m o t i v a t i o n a l b e h a v i o r s i n the opossum, D i d e l p h i s v i r g i n i a n a . J . Comp. P h y s i o l . P s y c h o l . 64: 1-15. Romaniuk, A. 1963. E m o t i o n a l r e s p o n s e s evoked by h y p o t h a l a m i c s t i m u l a t i o n i n c a t s . B u l l . Acad. P o l o n . S c i . Ser. s c i . b i o l . 11: 437-440. Romaniuk, A. 1964. The f o r m a t i o n o f d e f e n s i v e c o n d i t i o n e d r e f l e x e s by d i r e c t s t i m u l a t i o n o f the h y p o t h a l a m i c " f l i g h t - p o i n t s " i n c a t s . A c t a B i o l . E x p e r . (Warsaw) 24: 145-151. Romaniuk, A. 1965. R e p r e s e n t a t i o n o f a g g r e s s i o n and f l i g h t r e a c t i o n s i n the hypothalamus o f t h e c a t . A c t a B i o l . E x p e r . 2_5: 177-186. Romaniuk, A. 1967. The r o l e o f the hypothalamus i n d e f e n s i v e b e h a v i o r . A c t a B i o l . E x p e r . (Warsaw) 27: 339-343. Ross, N., M. P i n e y r u a , S. P r i e t o , L. P. A r i a s , A. S t i r n e r and C. Galeano. 1965. C o n d i t i o n i n g o f m i d b r a i n b e h a v i o r a l r e s p o n s e s . Exp. N e u r o l . ll: 263-276. R o u t t e n b e r g , A. 1970. Hippocampal a c t i v i t y and b r a i n s t e m loci. J . Comp. P h y s i o l . P s y c h o l . 7_2: 161-170.  reward-aversion  Sano, K., Y. Mayanagi, H. S e k i n o , M. Ogashiwa and B. I s h i j i m a . 1970. R e s u l t s of s t i m u l a t i o n and d e s t r u c t i o n o f t h e p o s t e r i o r h y p o t h a l a mus i n man. J . N e u r o s u r g . 33_: 689-707.  - 65 -  S i e g e l , A. and D. Skog. 1970. Effects of e l e c t r i c a l stimulation of the septum upon attack behavior e l i c i t e d from the hypothalamus i n  the cat. Brain Res. 23: 371-380. S i l v e s t r i n i , B. 1958. Neuropharmacological study of the central effects of benactyzine and hydroxyzine (cerebral e l e c t r i c a l a c t i v i t y , alarm and f l i g h t reaction on hypothalamic stimulation, c e n t r a l antagonisms). Arch. Internat. Pharmacodyn. 116: 71-85. Skultety, F. M. 1963. Stimulation of periaqueductal gray and hypothalamus. Arch. Neurol. (Chicago) 8.: 608-620. Sokal, R. R. and F. J. Rohlf. 1969. "Biometry."  Freeman, San Francisco.  Spiegel, E. A., M. K l e t z k i n and E. G. Szekely. 1954. Pain reactions upon stimulation of the tectum mesencephali. J . Neuropath. JJ3: 212-220. Stein, L. 1965. F a c i l i t a t i o n of avoidance behavior by p o s i t i v e brain s t i mulation. J . Comp. P h y s i o l . Psychol. 60_: 9-19. S t e l l a r , E. 1954. The physiology of motivation.  Psychol. Rev. 6_1: 5-22.  S t e l l a r , E. 1960. Drive and motivation, pp. 1501-1527. In "Handbook of Physiology, S e c t . l , Neurophysiology," Vol._3. J . F i e l d (ed.). American P h y s i o l o g i c a l Society, Washington, D.C. Stokman, C. L. J . and M. Glusman. 1968. A procedure to quantify hypothalam i c a l l y e l i c i t e d agonistic behavior i n the cat. Psychon. S c i . 11:  325-326.  Stokman, C. L. J . and M. Glusman. 1969. Suppression of hypothalamically produced f l i g h t responses by punishment. Physiol. Behav. 4:  523-525.  Stokman, C. L. J . and M. Glusman. 1970. Amygdaloid modulation of hypothalamic f l i g h t i n cats. J . Comp. P h y s i o l . Psychol. 7JL: 365-375. Thompson, R. F. 1967. "Foundations of P h y s i o l o g i c a l Psychology." Harper and Row, New York. Val'dman, A. V. and M. M. Kozlovskaya. 1970. Experimental study of the t r a n q u i l i z i n g and antidepressant action of the central cholinol y t i c s . B u l l . Exper. B i o l . Med. 69: 48-52. Valenstein, E. S. 1964. Problems of measurement and i n t e r p r e t a t i o n with r e i n f o r c i n g brain stimulation. Psychol. Rev. 71: 415-437.  - 66 -  V a l e n s t e i n , E . S. 1966. The a n a t o m i c a l locus o f Prog. P h y s i o l . P s y c h o l . 1: 149-190. V a l e n s t e i n , E . S. 1969. B e h a v i o r e l i c i t e d B r a i n Behav. E v o l . 2: 295-316.  reinforcement.  by h y p o t h a l a m i c  V a l e n s t e i n , E . S. 1971. C h a n n e l i n g o f r e s p o n s e s e l i c i t e d stimulation. J . P s y c h i a t . Res. 8_: 335-344.  stimulation.  by h y p o t h a l a m i c  V a l e n s t e i n , E . S., V. C. Cox and J . W. K a k o l e w s k i , 1969. The h y p o t h a l a mus and m o t i v a t e d b e h a v i o r , pp. 242-285. I n "Reinforcement and B e h a v i o r . " J . T. Tapp ( e d . ) . Academic P r e s s , New York. V a l e n s t e i n , E. S., V. C. Cox and J . W. K a k o l e w s k i . 1970. Re-examination of the r o l e o f the hypothalamus i n m o t i v a t i o n . P s y c h o l . Rev. 77: 16-31. V a l i n s , S. 1970. The p e r c e p t i o n and l a b e l i n g o f b o d i l y changes as d e t e r m i nants of e m o t i o n a l b e h a v i o r , pp. 229-243. I n " P h y s i o l o g i c a l C o r r e l a t e s of E m o t i o n . " P. B l a c k ( e d . ) . Academic P r e s s , New York. Vergnes, M. and P. K a r l i . 1970. Declenchement d'un comportement d ' a g r e s s i o n par s t i m u l a t i o n S l e c t r i q u e de 1'hypothalamus median chez l e r a t . P h y s i o l . Behav. 5: 1427-1430. Wada, J . A. and H. Ikeda. 1966. The s u s c e p t i b i l i t y to a u d i t o r y s t i m u l i o f animals t r e a t e d w i t h m e t h i o n i n e s u l f o x i m i n e . Exp. N e u r o l . 15: 157-165. Wada, J . A. and M. Matsuda. 1970. Can h y p o t h a l a m i c a l l y induced escape beh a v i o r be c o n d i t i o n e d ? Exp. N e u r o l . 28_: 502-512. Wada, J . A., M. Matsuda, E . Jung and A. E. Hamm. 1970. M e s e n c e p h a l i c a l l y induced escape b e h a v i o r and avoidance performance. Exp. N e u r o l . 29: 215-220. Wasman, M. and J . P. F l y n n . 1962. D i r e c t e d a t t a c k e l i c i t e d thalamus. A r c h . N e u r o l . (Chicago) 6_: 220-227. Wolfle,  from the hypo-  T. L., D. J . Mayer, B. Carder and J . C. L i e b e s k i n d . 1971. M o t i v a t i o n a l e f f e c t s of e l e c t r i c a l s t i m u l a t i o n i n d o r s a l tegmentum o f the rat. P h y s i o l . Behav. 7_: 569-574.  Woodworth, C. H. 1971. A t t a c k e l i c i t e d i n r a t s by e l e c t r i c a l s t i m u l a t i o n o f the l a t e r a l hypothalamus. P h y s i o l . Behav. 6_: 345-353.  Yasukochi, G. 1960. Emotional responses e l i c i t e d by e l e c t r i c a l stimulation of the hypothalamus i n cat. F o l i a Psychiatr. Neurol. Jap. 14: 260-267.  

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0101727/manifest

Comment

Related Items