Open Collections

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Effects of localized brain stimulation on conditioned taste aversion in rats LePiane, Fredric Gene 1977

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

Notice for Google Chrome users:
If you are having trouble viewing or searching the PDF with Google Chrome, please download it here instead.

Item Metadata

Download

Media
831-UBC_1978_A8 L46.pdf [ 3.3MB ]
Metadata
JSON: 831-1.0094431.json
JSON-LD: 831-1.0094431-ld.json
RDF/XML (Pretty): 831-1.0094431-rdf.xml
RDF/JSON: 831-1.0094431-rdf.json
Turtle: 831-1.0094431-turtle.txt
N-Triples: 831-1.0094431-rdf-ntriples.txt
Original Record: 831-1.0094431-source.json
Full Text
831-1.0094431-fulltext.txt
Citation
831-1.0094431.ris

Full Text

EFFECTS OF LOCALIZED BRAIN STIMULATION ON CONDITIONED TASTE AVERSION IN RATS by FREDRIC GENE LEPIANE B.A., U n i v e r s i t y o f Montana, 1973 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF ARTS i n THE FACULTY OF GRADUATE STUDIES (Department of P s y c h o l o g y ) 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 t h e r e q u i r e d s t a n d a r d THE UNIVERSITY OF BRITISH COLUMBIA November, 1977 F r e d r i c Gene L e p i a n e , 1977 0 . In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of Brit ish Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the Head of my Department or by his representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of P s y c h o l o g y  The University of Brit ish Columbia 2075 W e s b r o o k P l a c e V a n c o u v e r , C a n a d a V6T 1W5 Date 15 November 1977 i i ABSTRACT E f f e c t s of L o c a l i z e d B r a i n S t i m u l a t i o n on C o n d i t i o n e d T a s t e A v e r s i o n i n R a t s by F r e d r i c Gene L e P i a n e C o n d i t i o n e d t a s t e a v e r s i o n s o c c u r i n r a t s i f i n g e s t i o n o f a n o v e l f l a v o r e d s o l u t i o n i s f o l l o w e d by t o x i c o s i s . P r e v i o u s s t u d i e s , e m p l o y i n g t h e t e c h n i q u e of l o c a l i z e d b r a i n s t i m u l a t i o n t o examine th e n e u r a l c o r r e l a t e s o f t h i s b e h a v i o r , have shown t h a t s t i m u l a t i o n a p p l i e d t o r e s t r i c t e d a r e a s of t h e l i m b i c system d i s r u p t s t h e subsequent a v e r s i o n . The p r e s e n t s e r i e s o f e x p e r i -ments c o n f i r m e d and extended t h e r e s u l t s o f e a r l i e r r e p o r t s , b u t c h a l l e n g e d t h e i n t e r p r e t a t i o n o f t h o s e r e s u l t s . Whereas th e d e f i c i t s i n t a s t e a v e r s i o n s were a t t r i b u t e d p r e v i o u s l y t o t h e d i s r u p t i o n of memory f u n c t i o n s , t h e p r e s e n t e x p e r i m e n t s showed t h a t s u c h l e a r n i n g c o u l d i n f a c t o c c u r i n t h e p r e s e n c e o f l o c a l i z e d e l e c t r i c a l s t i m u l a t i o n o f t h e b r a i n (ESB). I t was c o n c l u d e d t h a t ESB may have cue p r o p e r t i e s s i m i l a r t o t h o s e o f a n o v e l f l a v o r , r e s u l t i n g i n a c o n d i t i o n e d a v e r s i o n t o " s t i m u l a t i o n - f l a v o r e d " w a t e r . Some o f t h e a p p a r e n t d e f i c i t s i n t a s t e a v e r s i o n l e a r n i n g c o u l d be r e i n t e r p r e t e d as r e s u l t s of s t i m u l u s c o n t r o l by t h e b r a i n s t i m u l a t i o n cue. E x p e r i m e n t I sought t o c o n f i r m e a r l i e r r e p o r t s o f t h e e f f e c t s of ESB o f t h e amygdala (a complex o f n u c l e i i n t h e l i m b i c system) on c o n d i t i o n e d t a s t e a v e r s i o n (CTA) and t o e x t e n d t h e s e f i n d i n g s t o two n u c l e i of t h e e x t r a -p y r a m i d a l system, t h e c a u d a t e and s u b s t a n t i a n i g r a , p r i m a r i l y a s s o c i a t e d w i t h motor f u n c t i o n s . These e f f e c t s were compared w i t h t h e e f f e c t s of ESB on a p a s s i v e a v o i d a n c e r e s p o n s e , i n o r d e r t o o b s e r v e t h e r e s u l t o f s i m i l a r t r e a t -ments on a n o t h e r t a s k r e q u i r i n g t h e a n i m a l s t o w i t h h o l d r e s p o n d i n g . ESB i i i applied to any of the three s i t e s during a c q u i s i t i o n of the passive avoidance behavior produced d e f i c i t s i n the response when tested 24 hr l a t e r . ESB applied during taste aversion conditioning, however, produced d e f i c i t s i n the subsequent CTA, tested 48 hr l a t e r , only when the amygdala was stimulated. These r e s u l t s suggested that the e f f e c t s of l o c a l i z e d extrapyramidal stimu-l a t i o n on passive avoidance behavior do not generalize to taste aversion. Experiment II sought to examine i n greater d e t a i l the nature of the ef f e c t s of amygdaloid stimulation on CTA. Stimulation applied while r a t s were drinking a novel s o l u t i o n (saccharin), during the time i n t e r v a l a f t e r the withdrawal of the solut i o n , or immediately a f t e r the i n j e c t i o n of the toxin, (lithium chloride) produced d e f i c i t s i n the subsequent CTA. Stimulation applied during the saccharin drinking i n the 48-hr r e t e s t , or during saccharin drinking both i n the conditioning and i n the ret e s t sessions, did not reduce the aversion to saccharin. The l a t t e r r e s u l t s suggested that taste aversion learning could occur i n the presence of concurrent ESB and implied that memory processes also may have been i n t a c t i n Experiment I. Experiment I I I sought to examine the p o s s i b i l i t y that amygdaloid stimu-l a t i o n may act as a cue or conditioned stimulus i n a taste aversion paradigm. Rats were stimulated while drinking unflavored water and injected with l i t h i u m 10 min l a t e r . When retested a f t e r 48 hr, with stimulation applied during water presentation, water intake was suppressed by 60%. Water intake, retested with concurrent ESB at subsequent 48^hr i n t e r v a l s , recoverd to the pre-lithium l e v e l by the eighth day a f t e r conditioning. This recovery appeared to be a function of the e x t i n c t i o n of a conditioned aversion, s i m i l a r to that seen i n a group of animals with an aversion conditioned to saccharin. Water intake i n the intervening days was unaffected, suggesting that an aversion had been conditioned to "stimulation-flavored" water and not simply to unflavored water. Unpoisoned and unstimulated controls showed no systematic suppression nor d i d c a u d a t e c o n t r o l s . These r e s u l t s s u g g e s t t h a t a m y g d a l o i d s t i m u l a t i o n p r o v i d e d a cue f o r l i t h i u m i l l n e s s , and i n E x p e r i m e n t I I an a v e r s i o n was c o n d i t i o n e d t o a s t i m u l u s compound c o n s i s t i n g o f t a s t e and s t i m u l a t i o n e l e m e n t s . Anthony G. P h i l l i p s V CONTENTS INTRODUCTION 1 ^ GENERAL METHOD 9 C o n d i t i o n e d T a s t e A v e r s i o n 10 Stepdown Shock A v o i d a n c e 11 EXPERIMENT I . COMPARISON BETWEEN TASTE AVERSION AND SHOCK AVOIDANCE ... 13 Method 14 R e s u l t s 16 D i s c u s s i o n 27 EXPERIMENT I I . TASTE AVERSION WITH AMYGDALOID STIMULATION DURING VARIOUS PHASES OF CONDITIONING AND RETENTION 29 Method 29 R e s u l t s 31 D i s c u s s i o n 38 EXPERIMENT I I I . ELECTRICAL STIMULATION OF THE AMYGDALA AS A CONDITIONED STIMULUS FOR TASTE AVERSION 43 Method 43 R e s u l t s 45 D i s c u s s i o n 52 GENERAL DISCUSSION 54 REFERENCES 58 v i L I S T OF TABLES T a b l e 1. T a s t e a v e r s i o n p e r c e n t a g e s c o r e s , means (+stand a r d e r r o r s ) 24 T a b l e 2. Mean (+ s t a n d a r d e r r o r ) w a t e r and s a c c h a r i n i n t a k e i n Ex p e r i m e n t I I 37 T a b l e 3. Mean ( + s t a n d a r d e r r o r ) w a t e r and s a c c h a r i n i n t a k e i n E x p e r i m e n t I I I 51 v i i L I ST OF FIGURES F i g u r e 1. E l e c t r o d e p l a c e m e n t s i n t h e t h r e e s t i m u l a t i o n s i t e s o f E x p e r i m e n t I 18 F i g u r e 2. Mean i n t a k e o f w a t e r and s a c c h a r i n i n E x p e r i m e n t I 20 F i g u r e 3. S a c c h a r i n i n t a k e i n t h e f o u r r e t e s t s , e x p r e s s e d as p e r c e n t a g e o f i n t a k e d u r i n g t h e c o n d i t i o n i n g s e s s i o n , p r i o r t o L i C l i n j e c t i o n i n E x p e r i m e n t I 22 F i g u r e 4. The e f f e c t s o f ABL, CD, and SNC s t i m u l a t i o n on a c q u i s i t i o n and r e t e n t i o n o f stepdown p a s s i v e a v o i d a n c e 26 F i g u r e , 5. E l e c t r o d e p l a c e m e n t s o f t h e s i x ABL groups t e s t e d i n E x p e r i m e n t I I 33 F i g u r e 6. S a c c h a r i n i n t a k e i n t h e r e t e n t i o n t e s t , e x p r e s s e d as p e r c e n t a g e of o f i n t a k e d u r i n g c o n d i t i o n i n g , p r i o r t o L i C l i n j e c t i o n i n E x p e r i m e n t I I 35 F i g u r e 7. E l e c t r o d e p l a c e m e n t s o f t h e t h r e e ABL and t h r e e CD groups i n E x p e r i m e n t I I I 47 F i g u r e 8. F l u i d i n t a k e i n t h e f o u r r e t e s t s , e x p r e s s e d as p e r c e n t a g e o f i n i n t a k e d u r i n g c o n d i t i o n i n g , p r i o r t o L i C l o r N a C l i n j e c t i o n i n E x p e r i m e n t I I I 49 v i i i ACKNOWLEDGEMENTS I am i n d e b t e d t o Dr. Anthony P h i l l i p s f o r h i s s u g g e s t i o n s r e g a r d i n g t h e c o n c e p t i o n and d e s i g n o f t h e s e e x p e r i m e n t s , and f o r h i s dogged encouragement t h r o u g h o u t t h e p r e p a r a t i o n o f t h e m a n u s c r i p t . I am a l s o g r a t e f u l t o Dr. Donald W i l k i e f o r h i s i n s i g h t f u l c r i t i c i s m , w h i c h c o n t r i b u t e d e x t e n s i v e l y t o t h e f i n a l f o r m o f t h e major arguments. T h i s r e s e a r c h was s u p p o r t e d by t h e N a t i o n a l R e s e a r c h C o u n c i l o f Canada g r a n t (67-7808) t o Dr. P h i l l i p s . 1 INTRODUCTION I t i s f i r m l y e s t a b l i s h e d t h a t when t h e con s u m p t i o n o f a n o v e l f o o d i s f o l l o w e d by a s t a t e o f i n t e r n a l m a l a i s e , an a n i m a l l e a r n s t o a v o i d t h a t f o o d i n subsequent e n c o u n t e r s ( R z o s k a , 1953; G a r c i a , H a n k i n s , and R u s i n i a k , 1974; G a r c i a , K i m e l d o r f , and K o e l l i n g , 1955). I n mammals, a s t r o n g a v e r s i o n i s formed a f t e r a s i n g l e e x p e r i e n c e o f f o o d p o i s o n i n g , i f t h e t a s t e and i l l n e s s cues a r e s u f f i c i e n t l y s a l i e n t (Revusky, and G a r c i a , 1970). I n t h i s manner, t h e o r g a n i s m q u i c k l y l e a r n s t o a v o i d f o o d s h a r m f u l t o i t s i n t e r n a l s t a t e , i n much t h e same way as i t l e a r n s t o a v o i d s t i m u l i , s u c h as v i s u a l o r a u d i t o r y c u e s , w h i c h p r e d i c t e x t e r n a l d a n g e r s , such as p r e d a t o r s o r p h y s i c a l h a z a r d s . W h i l e t h e r e can be no q u e s t i o n o f t h e a d a p t i v e s i g n i f i c a n c e o f l e a r n e d f o o d a v e r s i o n s , t h e y appear t o d i f f e r i n some i m p o r t a n t r e s p e c t s from .^avoidance r e s p o n s e s c o n d i t i o n e d t o cues t h a t p r e d i c t n o x i o u s e x t e r o c e p t i v e s t i m u l i . The most s t r i k i n g d i f f e r e n c e r e l a t e s t o t i m e s c a l e : f o o d a v e r s i o n s can be e s t a b -l i s h e d when con s u m p t i o n and i l l n e s s a r e s e p a r a t e d by s e v e r a l h o u r s (Revusky, 1968; Revusky and G a r c i a , 1970; S m i t h and R o l l , 1967); t h i s i s n o t t h e c a s e w i t h v i s u a l o r a u d i t o r y cues and p e r i p h e r a l d i s c o m f o r t . F u r t h e r m o r e , t h e s e n s o r y m o d a l i t i e s by w h i c h t h e f o o d and i l l n e s s s t i m u l i a r e p e r c e i v e d a r e c r i t i c a l f o r t h e e s t a b l i s h m e n t o f l e a r n e d f o o d a v e r s i o n s . I n r a t s , f o r example, n o v e l g u s t a t o r y s t i m u l i can be a s s o c i a t e d r e a d i l y w i t h i l l n e s s b u t not w i t h e l e c t r i c f o o t s h o c k (Braneman and C a p r e t t a , 1965; D i e t z and C a p r e t t a , 1967; G a r c i a and K o e l l i n g , 1966), a l t h o u g h K r a n e and Wagner"s (1975) d a t a s u g g e s t t h a t t h i s d i f f e r e n c e may be p a r t l y a f u n c t i o n o f t h e t i m e i n t e r v a l between cue and consequence. On t h e o t h e r hand, v i s u a l and a u d i t o r y cues can be a s s o c i a t e d r e a d i l y w i t h f o o t s h o c k , b u t n o t w i t h g a s t r o - i n t e s t i n a l m a l a i s e ( G a r c i a and K o e l l i n g , 1966; L a r s e n and Hyde, 1977; M o r r i s o n and C o l l y e r , 1 9 7 4 ) . The r o l e o f s e n s o r y m o d a l i t i e s i n f o o d a v e r s i o n s may be s p e c i e s - s p e c i f i c , as 2 t h e q u a i l a s s o c i a t e s i l l n e s s more s t r o n g l y w i t h v i s u a l cues t h a n w i t h g u s t a t o r y cues ( W i l c o x o n , D r a g o i n , and K r a i , 1971). On t h e b a s i s of t h e s e d a t a , G a r c i a and c o - w o r k e r s s u g g e s t e d t h a t i n mammals t h e n e u r a l mechanisms r e s p o n s i b l e f o r a s s o c i a t i n g t a s t e s t i m u l i w i t h i l l n e s s a r e i n d e p e n d e n t f r o m t h e systems w h i c h s u b s e r v e t h e a s s o c i a t i o n o f e x t e r o c e p t i v e cues w i t h c u t a n e o u s p a i n ( G a r c i a and K o e l l i n g , 1966; G a r c i a , H a n k i n s , and R u s i n i a k , 1974). T h i s h y p o t h e s i s has r e c e i v e d some s u p p o r t f r o m l e s i o n s t u d i e s i n w h i c h t h e e f f e c t s o f l o c a l i z e d b r a i n damage on c o n d i t i o n e d t a s t e a v e r s i o n (CTA)' have been compared w i t h t h e e f f e c t s on shock a v o i d a n c e o r c o n d i t i o n e d s u p p r e s s i o n . R a t s w i t h n e a r l y t o t a l h i p p o c a m p a l l e s i o n s have been shown t o be i m p a i r e d on a p a s s i v e a v o i d a n c e r e s p o n s e t o f o o t s h o c k , b u t not on a c o n d i t i o n e d a v e r s i o n t o sweet t a s t e s ( M i l l e r , E l k i n s , F r a s e r , P e a c o c k , and Hobbs, 1975; Murphy and Brown, 1974). I n a n o t h e r r e p o r t , however, s u c h l e s i o n s r e s u l t e d i n a m i l d d i s r u p t i o n o f a c o n d i t i o n e d a v e r s i o n t o a f a m i l i a r s a c c h a r i n s o l u t i o n ( M i l l e r , E l k i n s , and P e a c o c k , 197>1>). L e s i o n s o f t h e v e n t r a l hippocampus d i s r u p t e d t h e a c q u i s i t i o n o f a c o n d i t i o n e d e m o t i o n a l r e s p o n s e (GER) t o a w h i t e n o i s e s i g n a l f o l l o w e d by f o o t s h o c k (McGowan, H a n k i n s , and G a r c i a , 1972). ' Such l e s i o n s a l s o d i s r u p t e d a p a s s i v e a v o i d a n c e o f a b l a c k compartment where f o o t s h o c k had been a d m i n i s t e r e d ( B e s t and O r r , 1 9 7 3 ) . B o t h s t u d i e s r e p o r t e d t h a t a CTA t o a n o v e l s a c c h a r i n s o l u t i o n was n o t r e d u c e d by v e n t r a l h i p p o c a m p a l l e s i o n s , a l t h o u g h McGowan e t a l . (1972) r e p o r t e d an a p p a r e n t enhancement o f t h e a v e r s i o n t o t h e weaker s a c c h a r i n c o n c e n t r a t i o n a f t e r r e p e a t e d c o n d i t i o n i n g t r i a l s . I n g e n e r a l , however, h i p p o c a m p a l l e s i o n s d i s r u p t a v o i d a n c e r e s p o n s e s c o n d i t i o n e d t o v i s u a l and a u d i t o r y cues f o l l o w e d by f o o t s h o c k , b u t have l i t t l e e f f e c t on a v e r s i o n s c o n d i t i o n e d t o t a s t e cues f o l l o w e d by i l l n e s s i n r a t s . S e p t a l l e s i o n s p r o d u c e d e f i c i t s i n p a s s i v e a v o i d a n c e ( M c C l e a r y , 1966) and i n CER l e a r n i n g (McGowan e t a l . , 1 972), but n o t i n t a s t e a v e r s i o n l e a r n i n g 3 ( H a m i l t o n and C a p o b i a n c o , 1973; Hobbs, E l k i n s , and P e a c o c k , 1974; McGowan e t a l a l . , 1 972). The a p p a r e n t enhancement o f t h e a c q u i s i t i o n o f CTA w i t h s e p t a l and e s p e c i a l l y w i t h m e d i a l s e p t a l l e s i o n s ( H a m i l t o n and C a p o b i a n c o , 1973; McGowan, G a r c i a , E r v i n , and S c h w a r t z , 1969; McGowan e t a l . , 1972) and t h e more r a p i d e x t i n c t i o n w i t h m e d i a l s e p t a l l e s i o n s ( S i e g e l , 1976) may be due t o t h e i n c r e a s e d r e a c t i v i t y t o t a s t e and n e g a t i v e p o s t i n g e s t i v e cues r e p o r t e d by B e a t t y and Schwartzbaum (1968) and H a m i l t o n and Capobianco ( 1 9 7 3 ) . L e s i o n s o f t h e l a t e r a l hypothalamus (LH) p r o d u c e d e f i c i t s b o t h i n shock escape and a v o i d a n c e and i n f o o d a v e r s i o n s ( C o s c i n a and B a l a g u r a , 1970; R o t h , S c h w a r t z , and T e i t e l b a u m , 1973; R u n n e l s and Thompson, 1969; Schwartz and T e i t e l b a u m , 1974). However, r a t s w i t h s u c h l e s i o n s q u i c k l y r e c o v e r a p r e v i o u s l y - l e a r n e d CTA ( S c h w a r t z and T e i t e l b a u m , 1974) and may l e a r n new f o o d a v e r s i o n s s e v e r a l months a f t e r t h e l e s i o n ( R o t h e t a l . , 1 973). As w i t h f e e d i n g d e f i c i t s p r o d uced by LH l e s i o n s ( T e i t e l b a u m and E p s t e i n , 1 9 6 2 ) , i m p a i r m e n t s o f CTA o r shock a v o i d a n c e memory a r e d i f f i c u l t t o i n t e r p r e t because o f a p p a r e n t d i f f e r e n c e s i n t h e r a t e s o f r e c o v e r y of v a r i o u s p e r f o r -mance f u n c t i o n s (Devenport and B a l a g u r a , 1971; Schwartz and T e i t e l b a u m , 1974; T e i t e l b a u m and E p s t e i n , 1962). L e s i o n s of t h e amygdala complex have been shown t o p r o d u c e d e f i c i t s i n t h e a c q u i s i t i o n o f t a s t e a v e r s i o n s i n r a t s (Kemble and N a g e l , 1973; McGowan e t a l . , 1972; Nachman and Ashe, 1974; R o l l s and R o l l s , 1 9 7 3 a ) . T h i s e f f e c t , however, does n o t appear t o be t a s k - s p e c i f i c , as a m y g d a l o i d l e s i o n s a l s o i m p a i r a CER t o an a u d i t o r y s t i m u l u s (McGowan e t a l . , 1 9 7 2 ) , a v o i d a n c e o f mouthshock, p e r f o r m a n c e o f a DRL-20 s c h e d u l e f o r f o o d r e i n f o r c e m e n t , and a l t e r n a t i o n o f l e v e r - p r e s s i n g f o r f o o d r e i n f o r c e m e n t ( P e l l e g r i n o , 1 9 6 8 ) . The impairment of CTA, however, may be r e l a t e d t o t h e predominant use of a s i n g l e - b o t t l e ( " f o r c e d - c h o i c e " ) t r a i n i n g p r o c e d u r e . When t r a i n e d i n a two-b o t t l e ( " f r e e - c h o i c e " ) paradigm, r a t s w i t h a m y g d o l o i d l e s i o n s have been shown 4 to a c q u i r e an a v e r s i o n t o s u c r o s e as r a p i d l y as n o n l e s i o n e d c o n t r o l s ( M i k u l k a , Freeman, and L i d s t r o m , 1 9 7 7 ) , s u g g e s t i n g an i n t a c t a b i l i t y t o a s s o i c a t e a t a s t e s t i m u l u s w i t h v i s c e r a l d i s c o m f o r t . A l t h o u g h t h e a u t h o r s a t t r i b u t e t h e pe r f o r m a n c e d e f i c i t s seen i n a f o r c e d - c h o i c e p a r a d i g m t o an i n a b i l i t y t o i n h i b i t a p p r o a c h b e h a v i o r , t h e i r e x t i n c t i o n d a t a weaken t h i s v i e w : whether t r a i n e d i n f r e e - o r f o r c e d - c h o i c e p a r a d i g m s , l e s i o n e d a n i m a l s c o n t i n u e d t o a v o i d t h e t e s t s o l u t i o n a f t e r t e n t w o - b o t t l e e x t i n c t i o n t r i a l s . O ther r e p o r t s s u g g e s t t h a t i m p a i r m e n t s i n t h e p e r c e p t i o n o r i n t e r p r e t a t i o n o f r e l e v a n t s t i m u l i may c o n t r i b u t e t o t h e d e f i c i t s seen w i t h a m y g d a l o i d l e s i o n s ( R o l l s , and R o l l s , 1973b; P e l l i g r i n o , 1968). A n o t h e r a p p r o a c h t o t h e s t u d y o f t h e n e u r a l s u b s t r a t e s o f b o t h f o o d a v e r s i o n s and s h o c k - r e i n f o r c e d b e h a v i o r s has employed l o c a l i z e d e l e c t r i c a l s t i m u l a t i o n o f t h e b r a i n (ESB). The e f f e c t s o f t h i s p r o c e d u r e have been i n t e r p r e t e d as d i s r u p t i o n s o r m o d i f i c a t i o n s o f r e c e n t l y - a c q u i r e d a d a p t i v e r e s p o n s e s , p r e sumably by i n t e r f e r i n g i n some way w i t h memory ( f o r r e v i e w s , see K e s n e r and W i l b u r n , 1974; McGaugh and G o l d , 1976). I n many e x p e r i m e n t s u t i l i z i n g l o c a l i z e d ESB, memory i s d e f i n e d as a m u l t i c o m p o n e n t model i n w h i c h s t i m u l i a r e f i r s t encoded by a cue a c c e s s s ystem, s t o r e d i n e i t h e r s h o r t - t e r m o r l o n g - t e r m memory ( t h r o u g h a p r o c e s s o f c o n s o l i d a t i o n ) , and r e t r i e v e d on some l a t e r o c c a s i o n ( K e s n e r , 1977). K e s n e r and W i l b u r n (1974) have p r o p o s e d t h a t l o c a l i z e d s t i m u l a t i o n be a p p l i e d a t v a r i o u s phases o f a c q u i s i t i o n o r r e c a l l t o i d e n t i f y t h e n e u r a l s t r u c t u r e s i n v o l v e d i n t h e d i f f e r e n t components o f memory d e s c r i b e d above. What i s m i s s i n g from t h i s t y p e o f a n a l y s i s i s t h e p o s s i b i l i t y t h a t ESB may have s t i m u l u s p r o p e r t i e s . The f o l l o w i n g e x p e r i m e n t s t a k e t h i s p o s s i b i l i t y i n t o c o n s i d e r a t i o n . S e v e r a l s t u d i e s have r e p o r t e d t h e t e f f e c t s o f l o c a l i z e d ESB on CER and a c t i v e o r p a s s i v e a v o i d a n c e o f f o o t s h o c k . P o s t - t r i a l s t i m u l a t i o n o f r e g i o n s s u c h as t h e hippocampus ( B r u n n e r , R o s s i , S t u t z , and R o t h , 1970; K e s n e r and 5 Conner, 1972; Kes n e r and Doty, 1968), c a u d a t e n u c l e u s ( F i b i g e r and P h i l l i p s , 1976; Wyers and Deadwyler, 1971; Wyers, Peeke, W i l l i s t o n , and H e r z , 1 9 6 8 ) , s u b s t a n t i a n i g r a ( P h i l l i p s and C l o u s t o n , 1977; R o u t t e n b e r g and Holzman, 1 9 7 3 ) , thalamus (Mahut, 1962; W i l f r u r n and K e s n e r , 1972), and amygdala (B r e s n e h a n and R o u t t e n b e r g , 1972; Goddard, 1964; G o l d , H a f i r - i , and HcGaugh, 1973) has been shown t o d i s r u p t t h e memory c o n s o l i d a t i o n o r s t o r a g e o f t h e s e r e s p o n s e s . I n a s s e s s i n g t h e r o l e o f s p e c i f i c n e u r o a n a t o m i c a l r e g i o n s i n memory by means o f l o c a l i z e d b r a i n s t i m u l a t i o n , i t i s e s s e n t i a l t o d e t e r m i n e t h e p o s s i b l e i n v o l v e m e n t o f s e i z u r e a c t i v i t y . S e v e r a l s t u d i e s s u g g e s t t h a t t h e amnesic e f f e c t s o f s t i m u l a t i o n i n t h e hippocampus (Kapp, Kaufman, and R e p o l e , 1974; Shinkman and Kaufman, 1972) and amygdala (Goddard, 1972; L i d s k y , L e v i n e , K r e i n i c k , and Schwartzbaum, 1970) may be m e d i a t e d by s e i z u r e s . However, i t now i s w e l l - e s t a b l i s h e d t h a t l o c a l i z e d b r a i n s t i m u l a t i o n i n t h e hippocampus (Brunner et_ a l . , 1970; Kes n e r and Conner,-;,', 1972), c a u d a t e (Wyers and Deadw y l e r , 1973), amygdala (Bresnehan and R o u t t e n b e r g , 1972; G o l d e t a l . , 1 9 7 3 ) , and s u b s t a n t i a n i g r a ( R o u t t e n b e r g and Holzman, 1973) can pro d u c e a p p a r e n t amnesia i n t h e absence of b r a i n s e i z u r e s . R e t e n t i o n d e f i c i t s were a t t r i b u t e d t o t h e d i s r u p t i o n o f c o n s o l i d a t i o n o r s t o r a g e o f memory, as ESB was a d m i n i s t e r e d a f t e r f o o t s h o c k i n a l l c a s e s . A l t h o u g h t h e e f f e c t s o f l o c a l i z e d b r a i n s t i m u l a t i o n on t a s t e a v e r s i o n and s hock a v o i d a n c e have n o t been compared d i r e c t l y i n t h e same s t u d y , t h e v. p o s s i b l e d i s r u p t i v e e f f e c t s on CTA o f s t i m u l a t i o n a t a number of d i f f e r e n t s i t e s has been t h e s u b j e c t o f s e v e r a l r e c e n t e x p e r i m e n t s . I n one s u c h e x p e r i -ment, s t i m u l a t i o n o f t h e LH a p p l i e d f o r 6 h r a f t e r t h e c o n s u m p t i o n o f a l i t h i u m c h l o r i d e ( L i C l ) s o l u t i o n i m p a i r e d t h e g e n e r a l i z e d a v e r s i o n t o an i s o m o l a r sodium c h l o r i d e (NaCl) s o l u t i o n ( B a l a g u r a , R a l p h , and G o l d , 1972). L e t t and H a r l e y (1974) r e p o r t e d t h a t CTA was d i s r u p t e d when r a t s were a l l o w e d t o s e l f - a d m i n i s t e r b i l a t e r a l s t i m u l a t i o n ( " s e l f - s t i m u l a t i o n " ) o f t h e LH 6 c o n c u r r e n t l y w i t h t h e o n s e t o f i l l n e s s . S e l f - s t i m u l a t i o n a f t e r d r i n k i n g t h e n o v e l s o l u t i o n , b u t b e f o r e t h e o n s e t o f i l l n e s s , had no e f f e c t on t h e sub-sequent CTA. S i m i l a r r e s u l t s have been o b s e r v e d w i t h l o w - i n t e n s i t y , 25— microampere ( u A ) , b i l a t e r a l s t i m u l a t i o n o f t h e c o r t i c a l and m e d i a l n u c l e i o f t h e amygdala ( K e s n e r , Berman, B u r t o n , and H a n k i n s , 1975). S t i m u l a t i o n d e l i -v e r e d between a n o v e l t a s t e and an apomorphine i n j e c t i o n had no e f f e c t on t h e CTA d i s p l a y e d 72 h r l a t e r . S i m i l a r s t i m u l a t i o n a d m i n i s t e r e d e i t h e r 1 m i n , 30 m in, o r 3 h r a f t e r t h e o n s e t o f i l l n e s s d i s r u p t e d t h e development o f t a s t e a v e r s i o n . A r t h u r (1975) a l s o r e p o r t e d t h e impairment o f t a s t e a v e r s i o n l e a r n i n g by a m y g d a l o i d s t i m u l a t i o n , b u t i n t h i s i n s t a n c e , t h e c r i t i c a l t i m e f o r a d m i n i s t e r i n g t h e b r a i n s t i m u l a t i o n was t h e i n t e r v a l between t h e t a s t e cue and t h e o n s e t o f i l l n e s s . S t i m u l a t i o n d e l i v e r e d 15 min a f t e r an i n j e c -t i o n o f L i C l d i d n o t a l t e r t h e subsequent a v e r s i o n . These d i s c r e p a n t r e s u l t s may r e f l e c t p r o c e d u r a l d i f f e r e n c e s . I n t h e l a t t e r s t u d y , f o r example, t h e l o c u s o f s t i m u l a t i o n appeared t o c e n t e r on t h e l a t e r a l and b a s o l a t e r n u c l e i ; a l s o , h i g h - i n t e n s i t y s t i m u l a t i o n (115 uA) was employed. E x t e n d i n g t h e i r e a r l i e r o b s e r v a t i o n s , K e s n e r and Berman (1977) compared t h e e f f e c t s o f p o s t -i n j e c t i o n s t i m u l a t i o n o f t h e m i d b r a i n r e t i c u l a r f o r m a t i o n , hippocampus, and LH. T a s t e a v e r s i o n was n o t i m p a i r e d by s t i m u l a t i o n a t any o f t h e s e s i t e s . The f i n d i n g s w i t h h y p o t h a l a m i c s t i m u l a t i o n t h u s f a i l t o c o n f i r m t h e e a r l i e r r e p o r t s c i t e d above, a l t h o u g h t h i s may be a t t r i b u t e d t o t h e use o f apomorphine as t h e i l l n e s s - i n d u c i n g s t i m u l u s , o r t o t h e s h o r t e r d u r a t i o n o f t h e s t i m u l a t i n g c u r r e n t . Taken t o g e t h e r , t h e s e i n i t i a l e x p e r i m e n t s i n d i c a t e t h a t s t i m u l a t i o n o f the amygdala can d i s r u p t t h e memory o f t a s t e a v e r s i o n , p o s s i b l y by i n t e r f e r -i n g w i t h c o n s o l i d a t i o n o r s t o r a g e . When t h i s p o s s i b i l i t y i s c o u p l e d w i t h t h e l a r g e body of e v i d e n c e showing t h a t a m y g d a l o i d s t i m u l a t i o n a l s o may d i s -r u p t t h e memory of a v a r i e t y o f s h o c k - r e i n f o r c e d b e h a v i o r s , i t would appear 7 t o c o n t r a d i c t t h e h y p o t h e s i s t h a t CTA and shock a v o i d a n c e r e s p o n s e s a r e s u b s e r v e d by d i f f e r e n t n e u r a l systems ( B e s t a n d O r r , 1973; G a r c i a and K o e l l i n g , 1966; G a r c i a e t a l . , 1974). An a l t e r n a t i v e i n t e r p r e t a t i o n i s t h a t t h e e f f e c t s of l o c a l i z e d ESB on memory may r e v e a l r e g i o n s o f t h e b r a i n i n w h i c h s t i m u l a t i o n p r o d u c e s w i d e s p r e a d a l t e r a t i o n s i n n e u r a l a c t i v i t y ( G o l d , !'. H a n k i n s , and Rose, 1977). I t a p p e a r s t h a t t h e s u s c e p t i b i l i t y o f d i f f e r e n t r e g i o n s t o s u c h a l t e r a t i o n s may v a r y w i t h t h e t a s k under s t u d y . I f s o , t h e n e u r a l s u b s t r a t e s o f a g i v e n t a s k may be d e f i n e d by t h e s e n s i t i v i t y o f t h a t s u b s t r a t e t o i n t e r f e r e n c e by l o c a l i z e d ESB. The c u r r e n t d a t a i n d i c a t e t h a t t h e s u b s t r a t e s o f CTA and sh o c k a v o i d a n c e o v e r l a p i n t h e l i m b i c s ystem, i n an a r e a c e n t e r e d on t h e amygdala, as t h i s a r e a i s s e n s i t i v e t o t h e d i s r u p t i v e e f f e c t s o f ESB on b o t h t y p e s o f t a s k s . The i n i t i a l e x p e r i m e n t o f t h e p r e s e n t s t u d y was d e s i g n e d t o compare the e f f e c t s o f l o c a l i z e d ESB o f t h e amygdala and b a s a l g a n g l i a ( p a r t o f t h e e x t r a p y r a m i d a l motor system) on t a s t e a v e r s i o n and p a s s i v e a v o i d a n c e o f f o o t -shock i n r a t s . I t s h o u l d be n o t e d t h a t w h i l e many r e s e a r c h e r s r e f e r t o t h i s as an a v o i d a n c e p a r a d i g m i t may be more a p p r o p r i a t e t o d e f i n e i t as a p u n i s h -ment par a d i g m i n w h i c h t h e r e s p o n s e o f d e s c e n d i n g from t h e p l a t f o r m i s p u n i s h e d by f o o t s h o c k . The b a s o l a t e r a l n e u l e u s o f t h e amygdala (ABL) was c h o s e n , i n an a t t e m p t t o c o n f i r m r e p o r t s t h a t t h i s n u c l e u s i s i n v o l v e d i n b o t h t a s k s . The s p e c i f i c s t r u c t u r e s i n t h e e x t r a p y r a m i d a l system i n c l u d e d a r e t h e c a u d a t e n u c l e u s (CD) and s u b s t a n t i a n i g r a zona compacta (SNC). P r e v i o u s s t u d i e s have shown t h a t l o w - l e v e l , p r o l o n g e d s t i m u l a t i o n may d i s r u p t t h e c o n s o l i d a t i o n o r s t o r a g e o f a p a s s i v e a v o i d a n c e r e s p o n s e ( F i b i g e r and P h i l l i p s , 1976; R o u t t e n b e r g and Holzman, 1 9 7 3 ) , b u t no s t u d i e s have r e p o r t e d t h e e f f e c t s o f e x t r a p y r a m i d a l s t i m u l a t i o n on CTA. The t a s t e a v e r s i o n and shock a v o i d a n c e p r o c e d u r e s were i n t e n d e d t o prod u c e a s t r o n g a v e r s i o n o r a v o i d a n c e r e s p o n s e a f t e r a s i n g l e t r a i n i n g 8 s e s s i o n . ESB was a p p l i e d t o d i f f e r e n t groups o f r a t s a t comparable phases i n th e a c q u i s i t i o n o f each t a s k . Thus, some a t t e m p t was made t o match t h e two p r o c e d u r e s w i t h r e s p e c t t o t h e number o f t r a i n i n g s e s s i o n s as w e l l as d u r a t i o n and i n t e n s i t y o f ESB. There were, however, i m p o r t a n t d i f f e r e n c e s i n t h e r e l a t i o n s h i p between ESB and t h e c r i t i c a l r e s p o n s e i n e a c h t a s k . I n t h e CTA parad i g m t h e a n i m a l had t o l e a r n t o s u p p r e s s d r i n k i n g . ESB was d e l i v e r e d p r e d o m i n a n t l y i n t h e p r e s e n c e o f t h i s r e s p o n s e d u r i n g a c q u i s i t i o n . The c r i t i c a l r e s p o n s e i n t h e p a s s i v e a v o i d a n c e s i t u a t i o n was t h e d e s c e n t f r o m t h e p l a t f o r m . Because i t h i s was an i n f r e q u e n t r e s p o n s e , ESB was n o t as c l o s e l y r e l a t e d t o i t as i t was t o d r i n k i n g i n t h e CTA paradigm.. . The p r o c e d u r e s a l s o d i f f e r e d i n some o t h e r i m p o r t a n t r e s p e c t s , s u c h as w a t e r d e p r i v a t i o n , l e n g t h o f t r a i n i n g and r e t e s t s e s s i o n s , and i n t e r v a l between a c q u i s i t i o n and r e t e s t s e s s i o n s . A f t e r comparing t h e e f f e c t s o f ESB on t h e s e two a v o i d a n c e r e s p o n s e s , a d d i t i o n a l e x p e r i m e n t s were c a r r i e d o u t t o examine i n g r e a t e r d e t a i l t h e t e m p o r a l p a r a m e t e r s o f d e l i v e r i n g ESB f o r i m p a i r i n g CTA. I n p a r t i c u l a r , t h e f o l l o w i n g s t u d i e s a p p l i e d t h e p a r a m e t r i c t e c h n i q u e s s u g g e s t e d by K e s n e r and W i l b u r n (.1974) i n o r d e r t o c l a r i f y t h e s p e c i f i c e f f e c t s o f ESB on memory s t o r a g e and r e t r i e v a l mechanisms. The r e s u l t s o f t h e s e e x p e r i m e n t s w i l l be d i s c u s s e d i n terms of t h e i r p o s s i b l e i m p l i c a t i o n s f o r t a s t e a v e r s i o n l e a r n i n g and f o r t h e r o l e o f ESB i n c o n d i t i o n i n g and memory. 9 GENERAL METHOD S u b j e c t s . M a l e W i s t a r a l b i n o r a t s (Woodlyn L a b o r a t o r i e s , G u e l p h -O n t a r i o ) , w e i g h i n g 250-350 g, were housed i n d i v i d u a l l y w i t h ad l i b a c c e s s t o l a b chow ( P u r i n a ) , ' and w a t e r . A f t e r r e c o v e r y f r o m s u r g e r y , a n i m a l s i n t h e CTA e x p e r i m e n t s were p l a c e d on a w a t e r d e p r i v a t i o n s c h e d u l e . A l i g h t - d a r k c y c l e o f 12 h r , a p p r o x i m a t i n g n o r m a l d a y - n i g h t h o u r s , was m a i n t a i n e d t h r o u g h -out t h e e x p e r i m e n t s . S u r g e r y . Each o f t h e i m p l a n t e d a n i m a l s was a n e s t h e t i z e d w i t h sodium p e n t o b a r b i t a l (Nembutal, 60 mg/kg). U s i n g a s t a n d a r d s t e r e o t a x i c i n s t r u m e n t w i t h t h e i n c i s o r b a r 5.0 mm above t h e i n t e r a u r a l l i n e , a b i p o l a r e l e c t r o d e (0.125 o r 0.250 mm; P l a s t i c P r o d u c t s , Roanoke, V i r g i n i a ) was l o w e r e d t o one of t h e a p p r o p r i a t e t a r g e t s and f i x e d t o t h e s k u l l w i t h j e w e l e r ' s s crews and a c r y l i c cement. The t a r g e t s and c o o r d i n a t e s were as f o l l o w s : (1) ABL (0.125 mm e l e c t r o d e ) , 0.8 mm p o s t e r i o r t o bregma, 4.8 mm l a t e r a l t o t h e s a g g i t a l s u t u r e , and 8.6 mm v e n t r a l t o t h e s k u l l s u r f a c e ; (2) CD (0.250 mm e l e c t r o d e ) , 1.0 mm a n t e r i o r , 2.5 mm l a t e r a l , and 5.0 mm v e n t r a l ; (3) SNC (0.125 mm e l e c -t r o d e ) , 3.4 mm p o s t e r i o r , 2.5 mm l a t e r a l , and 7.5 mm v e n t r a l . A t l e a s t 10 days were a l l o w e d f o r r e c o v e r y from s u r g e r y . H i s t o l o g y . A l l i m p l a n t e d s u b j e c t s were s a c r i f i c e d w i t h e t h e r o r c a r b o n d i o x i d e gas and p e r f u s e d t r a n s c a r d i a l l y w i t h 0.9% N a C l f o l l o w e d by 10% b u f f e r e d n e u t r a l f o r m a l i n (Luna, 1968, P . 3 ) . The b r a i n s were removed a n d - f i x e d i n t h e f o r m a l i n s o l u t i o n f o r a t l e a s t 24 h r , f r o z e n , s e c t i o n e d a t 30 m i c r o n s and s t a i n e d a c c o r d i n g t o a m o d i f i e d K l u v e r - B a r r e r a method (Luna, 1968, pp. 203-204) f o r m y e l i n and n e r v e c e l l s . E l e c t r o d e p l a c e m e n t s were c o n f i r m e d by two ind e p e n d e n t o b s e r v e r s . D a t a o f s u b j e c t s w i t h e l e c t r o d e s o u t s i d e t h e t a r g e t a r e a s were not used i n t h e s t a t i s t i c a l a n a l y s i s . 10 C o n d i t i o n e d T a s t e A v e r s i o n A p p a r a t u s . A l l t e s t i n g was c a r r i e d out i n f i v e P l e x i g l a s chambers (21.5 x 30.5 x 45.5 cm h i g h ) , e a c h h a v i n g a 10 mm h o l e , 6 cm above t h e f l o o r , i n one of t h e n a rrow w a l l s . Water o r t h e s a c c h a r i n s o l u t i o n were d i s p e n s e d from g r a d u a t e d c y l i n d e r s f i t t e d w i t h c u r v e d , b a l l - t i p d r i n k i n g t u b e s ( A c t o Mfg. Co., Napa, C a l i f o r n i a ) . A c y l i n d e r was clamped t o t h e o u t s i d e of e ach t e s t i n g chamber so t h a t t h e t i p of t h e d r i n k i n g t u b e p r o j e c t e d t h r o u g h t h e h o l e and 3.5 cm i n t o t h e box;. A c c u r a t e measures of t h e volume of f l u i d consumed c o u l d be t a k e n by r e c o r d i n g t h e f l u i d l e v e l s i n t h e s e c y l i n -d e r s . Each t e s t chamber was p l a c e d i n a s e p a r a t e i n s u l a t e d e n c l o s u r e , v e n t i -l a t e d by a s m a l l f a n and i l l u m i n a t e d by a f l o r e s c e n t l i g h t . I n t r a c r a n i a l s t i m u l a t i o n was d e l i v e r e d t h r o u g h 80 cm l e a d s ( P l a s t i c P r o d u c t s ) , a t t a c h e d t o commutators and suspended from above t o a v o i d t a n g l i n g . F i v e c o n s t a n t c u r r e n t s t i m u l a t o r s were programmed t o d e l i v e r 60 Hz Ac t o t h e e l e c t r o d e s i n t r a i n s o f 3 sec d u r a t i o n , w i t h t h e c u r r e n t o f f f o r 6 sec between t r a i n s . P r o c e d u r e . F o r 6 d ays, a l l s u b j e c t s were h a b i t u a t e d t o a d e p r i v a t i o n s c h e d u l e under w h i c h t h e y were p e r m i t t e d t o d r i n k w a t e r f o r 10 min a t a p p r o x i -m a t e l y the same t i m e each day. A l l a n i m a l s were t r a n s p o r t e d t o and from t h e t e s t chambers i n p l a s t i c c a r r y i n g boxes p a r t i t i o n e d t o p r e v e n t p h y s i c a l c o n -t a c t between i n d i v i d u a l s . , C o n d i t i o n i n g was c a r r i e d out on t h e 7 t h day by p r e s e n t i n g a 0.2% (w/v) s a c c h a r i n s o l u t i o n d u r i n g t h e d r i n k i n g p e r i o d . A s i n g l e - b o t t l e p r o c e d u r e was used t h r o u g h o u t t h e s t u d y . I n t h e f i r s t e x p e r i m e n t , ESB (10 uA) was a d m i n i s -t e r e d t o t h e e x p e r i m e n t a l a n i m a l s w h i l e t h e t e s t s o l u t i o n was p r e s e n t ( e x c e p -t i o n s a r e n o t e d i n t h e P r o c e d u r e o f t h a t e x p e r i m e n t ) . Ten m i n u t e s a f t e r t h e r e m o v a l o f t h e s a c c h a r i n s o l u t i o n and t e r m i n a t i o n o f t h e s t i m u l a t i n g c u r r e n t , each a n i m a l was i n j e c t e d i n t r a p e r i t i o n e a l l y ( I P ) w i t h L i C l C.15M, 20 m l / k g ) . T h i s dose was s u f f i c i e n t t o i n d u c e symptoms o f i n t e r n a l m a l a i s e ( i m m o b i l i t y , f l a c c i d i t y , and d i a r r h e a ) f o r a t l e a s t 30 m i n i n a l l s u b j e c t s . F u r t h e r m o r e , t h i s s a c c h a r i n p l u s L i C l t r e a t m e n t has been shown t o produce a s t r o n g CTA a f t e r a s i n g l e c o n d i t i o n i n g s e s s i o n ( G a r c i a e t a l . , 1974; Nachman and Ashe, 1973). Water was p r e s e n t e d on t h e f o l l o w i n g day t o e n s u r e t h a t no g e n e r a l d r i n k i n g d e f i c i t was produced by t h e L i C l i n j e c t i o n . R e t e n t i o n o f t h e c o n d i t i o n e d a v e r s i o n t o s a c c h a r i n was t e s t e d on t h e 9 t h day by a l l o w i n g a c c e s s t o t h e s a c c h a r i n s o l u t i o n d u r i n g t h e d r i n k i n g p e r i o d . Low i n t a k e s o f t h e t e s t s o l u t i o n on t h i s day would i n d i c a t e t h a t an a v e r s i o n had been c o n d i t i o n e d by p a i r i n g t h e t a s t e w i t h t h e l i t h i u m i l l n e s s . E x t i n c t i o n o f t h e CTA was t e s t e d i n t h r e e a d d i t i o n a l d r i n k i n g s e s s i o n s (days 11, 13, and 1 5 ) , w i t h w a t e r a v a i l a b l e on days 10, 12, and 14. By m e a s u r i n g th e l e v e l o f s a c c h a r i n i n t a k e o v e r t h e 5 t e s t s days ( " c o n d i t i o n i n g " , " r e t e n -t i o n " , " e x t i n c t i o n 1-3"), i t was p o s s i b l e t o o b s e r v e t h e a c q u i s i t i o n and e x t i n c t i o n o f t h e CTA. Stepdown Shock A v o i d a n c e  A p p a r a t u s . T r a i n i n g and t e s t i n g was c a r r i e d o u t i n a P l e x i g l a s box (25 x 29 x 40.5 cm h i g h ) w i t h a p l a t f o r m (25 x 7 cm) e x t e n d i n g a c r o s s one o f the n a rrow ends, 7.5 cm above t h e f l o o r . The f l o o r was a g r i d made o f b r a s s r o d s , 3 mm i n d i a m e t e r , spaced 10 mm a p a r t . A r e l a y system was o p e r a t e d by a m i c r o s w i t c h under t h e p l a t f o r m , so t h a t a s c r a m b l e d 1 mA f o o t s h o c k was d e l i v e r e d t h r o u g h t h e g r i d f l o o r when an a n i m a l s t e p p e d down and r e l e a s e d t h e p l a t f o r m . When t h e p l a t f o r m was d e p r e s s e d by an a n i m a l ' s w e i g h t , a c o n t i n u o u s t r a i n o f e l e c t r i c a l c u r r e n t (60 Hz AC) was d e l i v e r e d t o t h e e l e c t r o d e by a s t i m u l a t o r and l e a d system s i m i l a r t o t h a t used i n t h e t a s t e a v e r s i o n e x p e r i -ment. The s w i t c h i n g c i r c u i t was c o n s t r u c t e d t o e n s u r e t h a t t h e f o o t s h o c k and 12 b r a i n - s t i m u l a t i o n c u r r e n t s were i s o l a t e d from one a n o t h e r . P r o c e d u r e . Each a n i m a l was h a b i t u a t e d t o h a n d l i n g f o r 3 days p r i o r t o t r a i n i n g by b e i n g p l a c e d i n t o t h e c a r r y i n g box f o r 3 min and r e t u r n e d t o t h e home cage. On t h e 4 t h day, t h e s u b j e c t s were t a k e n t o a t e s t i n g room where t h e y were t r a i n e d i n t h e stepdown a p p a r a t u s . As each a n i m a l was p l a c e d on t h e p l a t f o r m , a t i m e r was s t a r t e d m a n u a l l y . The t i m e t h a t e l a p s e d between p l a c i n g t h e a n i m a l on t h e p l a t f o r m and t h e d e s c e n t onto t h e g r i d f l o o r was r e c o r d e d as t h e " l a t e n c y o f f i r s t d e s c e n t " . The c r i t e r i o n f o r h a v i n g l e a r n e d to a v o i d t h e f o o t s h o c k was t h a t a s u b j e c t r e m a i n on t h e p l a t f o r m c o n t i n u o u s l y f o r 120 s e c . The t i m e t h a t e l a p s e d f r o m t h e i n i t i a l p lacement on t h e p l a t -f orm u n t i l t h e c r i t e r i o n was a t t a i n e d , was r e c o r d e d as t h e " t i m e t o r e a c h c r i t e r i o n " . The "number o f d e s c e n t s " b e f o r e t h e c r i t e r i o n was r e a c h e d was a l s o r e c o r d e d . One r a t t h a t f a i l e d t o r e a c h t h e c r i t e r i o n w i t h i n 10 min was c l a s s i f i e d as a " n o n - l e a r n e r " and dropped f r o m t h e e x p e r i m e n t . S t i m u l a t i o n was a p p l i e d t o t h e e l e c t r o d e of each r a t i n t h e ESB groups when i t had c l i m b e d b a c k onto t h e p l a t f o r m , f o l l o w i n g t h e f i r s t d e s c e n t . The s t i m u l a t i n g c u r r e n t was i n c r e a s e d from 0 uA t o 10 uA d u r i n g t h e 1 min on t h e p l a t f o r m , w i t h t h e two e x c e p t i o n s n o t e d i n E x p e r i m e n t I , T h i s i n t e n s i t y was t h e n d e l i -v e r e d whenever t h e a n i m a l was on t h e p l a t f o r m d u r i n g t h e t r a i n i n g s e s s i o n . R e t e n t i o n t e s t i n g f o r t h e p a s s i v e a v o i d a n c e r e s p o n s e t o o k p l a c e 24 h r a f t e r t r a i n i n g , b u t t h e i n t r a c r a n i a l s t i m u l a t i o n and f o o t s h o c k c u r r e n t s were t u r n e d o f f . The " l a t e n c y o f f i r s t d e s c e n t " from t h e p l a t f o r m was r e c o r d e d , as t h e measure of r e t e n t i o n . I f no d e s c e n t o c c u r r e d , t h e s u b j e c t was removed from t h e a p p a r a t u s a f t e r 3 min and a s s i g n e d a r e t e n t i o n s c o r e o f 180 s e c . T h i s t r a i n i n g p r o c e d u r e has been shown t o c o n d i t i o n a r e l i a b l e s hock a v o i d -ance r e s p o n s e i n c o n t r o l r a t s a f t e r a s i n g l e t r a i n i n g s e s s i o n (Bresnehan and R o u t t e n b e r g , 1972; F i b i g e r and P h i l l i p s , 1976; R o u t t e n b e r g and Holzman, 1973). EXPERIMENT I . COMPARISON BETWEEN TASTE AVERSION AND SHOCK AVOIDANCE. There i s some e v i d e n c e f r o m e x p e r i m e n t s on t h e d i s r u p t i v e e f f e c t s o f ESB w h i c h s u g g e s t s t h a t t h e n e u r a l s u b s t r a t e s o f v a r i o u s a v o i d a n c e t a s k s may d i f f e r . F o r example, t a s t e a v e r s i o n has been shown t o be i m p a i r e d o n l y by s t i m u l a t i o n i n c e r t a i n a r e a s o f t h e l i m b i c system, as d i s c u s s e d i n t h e I n t r o -d u c t i o n . On t h e o t h e r hand, shock a v o i d a n c e has been d i s r u p t e d by s t i m u l a t i o n a p p l i e d t o a v a r i e t y of s i t e s , i n c l u d i n g t h o s e i n t h e e x t r a p y r a m i d a l as w e l l as l i m b i c systems. I n o r d e r t o compare d i r e c t l y t h e n e u r a l c o r r e l a t e s behav-i o r i n t h e s e two t a s k s , s t i m u l a t i o n was a p p l i e d t o one l i m b i c and two e x t r a -p y r a m i d a l s i t e s , u s i n g s i m i l a r c u r r e n t p a r a m e t e r s . B r i e f l y , t h e a m y g d a l o i d complex was chosen as one s t i m u l a t i o n s i t e , b ecause s t i m u l a t i o n a p p l i e d t o t h i s a r e a o f t h e l i m b i c system has been shown t o d i s r u p t b o t h p a s s i v e shock a v o i d a n c e (Bresnehan and R o u t t e n b e r g , 1972; G o l d e t a l . , 1973) and c o n d i t i o n e d t a s t e a v e r s i o n (Kesner e t a l . , 1975; A r t h u r , 1975). I n t h e p r e s e n t e x p e r i m e n t , s t i m u l a t i o n was r e s t r i c t e d t o t h e ABL, s i n c e p r e v i o u s s t u d i e s s u g g e s t e d t h a t l e s i o n s o f t h e ABL p r o d u c e d i m p a i r m e n t s i n b o t h l e a r n i n g and r e t e n t i o n o f c o n d i t i o n e d t a s t e a v e r s i o n s , p o s s i b l y by i n h i b i t i n g t a s t e mechanisms ( R o l l s and R o l l s , 1973a, 1973b), B r e s n e h a n and R o u t t e n b e r g (1972) s u g g e s t e d t h a t r e t e n t i o n o f t h e stepdown t a s k was i m p a i r e d by s t i m u l a t i o n of t h e m e d i a l n u c l e u s b u t n o t t h e ABL. T h i s f i n d i n g s t a n d s i n c o n t r a s t t o t h e work o f G o l d e_t a l . ( 1 9 7 7 ) , N e v e r t h e l e s s , t h e p o s s i b i l i t y remained t h a t ABL s t i m u l a t i o n c o u l d have d i f f e r e n t i a l e f f e c t s on t h e s e two a v o i d a n c e r e s p o n s e s . Two e x t r a p y r a m i d a l (motor) s i t e s were a l s o s e l e c t e d , on t h e b a s i s o f p r e v i o u s s t u d i e s . R o u t t e n b e r g and Holzman (1973) r e p o r t e d t h a t s t i m u l a t i n g t h e SNC d u r i n g stepdown t r a i n i n g p r o duced poor r e t e n t i o n of t h e t a s k , when 14 r e t e s t i n g was done 24 h r l a t e r . A n i m a l s s t i m u l a t e d i n t h e CD a l s o showed i m p a i r e d r e t e n t i o n o f t h e stepdown a v o i d a n c e r e s p o n s e ( F i b i g e r and P h i l l i p s , 1 9 7 6 ), as w e l l as a s h o c k - i n d u c e d l i c k s u p p r e s s i o n (Wyers, Deadwyler, H i r a s u n a , and Montgomery, 1973). I n summary, t h e r e were two r e a s o n s f o r c h o o s i n g t h e CD and SNC s i t e s : t o r e p l i c a t e t h e p r e v i o u s e f f e c t s on t h e stepdown a v o i d a n c e t a s k , and, more i m p o r t a n t l y , t o o b s e r v e t h e e f f e c t s of CD and SNC s t i m u l a t i o n on t a s t e a v e r s i o n c o n d i t i o n i n g . Method S u b j e c t s and S u r g e r y . S i x t y r a t s were p r e p a r e d f o r t h e CTA p r o c e d u r e as d e s c r i b e d i n t h e G e n e r a l Method s e c t i o n . These were a s s i g n e d t o t h e f o l l o w i n g t r e a t m e n t g r o u p s : ABL (n=20), CD (n=10), SNC (n=20), and u n o p e r a t e d c o n t r o l s (UNOP, n=10), a l l o f w h i c h r e c e i v e d s a c c h a r i n p l u s L i C l . An u n o p e r a -t e d group, w h i c h r e c e i v e d s a c c h a r i n p l u s a s a l i n e i n j e c t i o n ( S A C - C n t l , n=7), was t e s t e d i n a n o t h e r e x p e r i m e n t , b u t t h e d a t a a r e i n c l u d e d h e r e f o r c o m p a r i -son. Three i m p l a n t e d a n i m a l s were e l i m i n a t e d b e f o r e t h e s t a r t o f t e s t i n g , as two d i e d and a n o t h e r l o s t i t s e l e c t r o d e a s sembly a f t e r s u r g e r y . P r o c e d u r e . I n t r a c r a n i a l s t i m u l a t i o n was a p p l i e d t o t h e i m p l a n t e d s u b j e c t s d u r i n g a c q u i s i t i o n t r a i n i n g i n b o t h of t h e t a s k s . I n t h e CTA p r o -c e d u r e , i m p l a n t e d s u b j e c t s were s t i m u l a t e d f o r 10 m i n , d u r i n g t h e p r e s e n t a t i o n of t h e s a c c h a r i n s o l u t i o n . The 60 Hz s i n e wave c u r r e n t was p u l s e d as d e s c r i b e d , w i t h t h e i n t e n s i t y s e t i n i t i a l l y a t 10 uA. F o r most o f t h e ABL s u b j e c t s , t h i s i n t e n s i t y e l i c i t e d b e h a v i o r s t h a t competed w i t h d r i n k i n g , s u c h as r e a r i n g , s n i f f i n g , and e x p l o r i n g . I n t h e s e c a s e s t h e c u r r e n t was r e d u c e d f r o m 10 uA u n t i l d r i n k i n g resumed. However, one a n i m a l was dropped from t h e e x p e r i m e n t a t t h i s t i m e , as i t d r a n k an a b n o r m a l l y s m a l l amount C2.4 ml) w i t h 2.0 uA s t i m u l a t i o n . The mean o f t h e r e m a i n i n g i n t e n s i t i e s a f t e r h i s t o l o g i c a l exam-i n a t i o n was 5.15 uA w i t h a r a n g e o f 2-10 uA. D u r i n g t r a i n i n g o f t h e stepdown t a s k , 10 uA ESB was a p p l i e d t o t h e i m p l a n t e d s u b j e c t s whenever t h e y were on t h e p l a t f o r m . A s m e n t i o n e d i n t h e G e n e r a l Method s e c t i o n , s t i m u l a t i o n was a p p l i e d c o n t i n u o u s l y e a c h t i m e a s u b j e c t r e t u r n e d onto t h e p l a t f o r m and f o r t h e e n t i r e 120 sec c r i t e r i o n p e r i o d . The d u r a t i o n o f t h e s t i m u l a t i n g c u r r e n t v a r i e d between r a t s , depend-i n g on t h e t o t a l l e n g t h o f t i m e s p e n t on t h e p l a t f o r m . T h i s may be e s t i m a t e d as 3-4 min, by n o t i n g t h e t i m e t o r e a c h c r i t e r i o n and number of d e s c e n t s i n F i g . 4. T h i s i s s i m i l a r t o t h e t o t a l d u r a t i o n (3 min , 20 sec ) r e c e i v e d by ea c h s u b j e c t i n t h e CTA p r o c e d u r e . I n two of t h e SNC s u b j e c t s , t h e 10 uA i n t e n s i t y e l i c i t e d motor r e s p o n -ses t h a t r e s u l t e d i n t h e i r f a l l i n g o f f t h e p l a t f o r m . When t h e c u r r e n t f o r t h e s e two was d e c r e a s e d t o 5 uA, t h e competing motor r e s p o n s e s c e a s e d and th e y r e a c h e d t h e a v o i d a n c e c r i t e r i o n . D a t a f o r t h e s e two r a t s wer^e a n a l y s e d w i t h t h o s e o f t h e r e s t o f t h e gro u p , s i n c e a l l a c q u i s i t i o n measures f e l l w i t h i n t h e range o f t h e o t h e r SNC s u b j e c t s . One c a u d a t e s u b j e c t t h a t f a i l e d t o r e a c h t h e a v o i d a n c e c r i t e r i o n was dropped from t h e e x p e r i m e n t . R e t e n t i o n was t e s t e d as d e s c r i b e d i n t h e G e n e r a l Method s e c t i o n . B r i e f l y , each a n i m a l was p l a c e d on t h e p l a t f o r m 24 h r a f t e r t r a i n i n g . The l a t e n c y o f t h e f i r s t d e s c e n t was r e c o r d e d , w i t h a maximum s c o r e o f 180 s e c . S i n c e i t has been s u g g e s t e d t h a t t h e amnesic e f f e c t s o f a m y g d a l o i d s t i m u l a t i o n may be m e d i a t e d by s e i z u r e s (Goddard, 1972; L i d s k y e t a l . , 1 9 7 0 ) , r e c o r d i n g s were made f%om th e ABL a f t e r t e s t i n g was c o m p l e t e d . U s i n g a s t i m u l a t o r s i m i l a r t o t h o s e i n t h e e x p e r i m e n t and a p o l y g r a p h ( G r a s s model 78D), an a n i m a l was s t i m u l a t e d f o r 3 sec a t an i n t e n s i t y o f 10 uA, w i t h 6 sec between s t i m u l a t i o n t r a i n s . When no a f t e r d i s c h a r g e s were o b s e r v e d , t h e i n t e n s i t y was i n c r e a s e d t o 20 uA, t h e n t o 30 uA w i t h o u t o b s e r v a b l e s e i z u r e a c t i v i t y . The e n t i r e s t i m u l a t i o n p e r i o d l a s t e d about 10 min, and t h e r e c o r d -i n g c o n t i n u e d f o r a n o t h e r 5 min. 16 A t t h e c o m p l e t i o n o f t h e e x p e r i m e n t , h i s t o l o g i c a l d a t a were c o l l e c t e d a c c o r d i n g t o t h e p r o c e d u r e a l r e a d y d e s c r i b e d . R e s u l t s H i s t o l o g y . The b r a i n s o f a l l i m p l a n t e d s u b j e c t s were examined, w i t h t h e e x c e p t i o n o f t h e f i v e r a t s m e n t i o n e d above. The 23 a n i m a l s j u d g e d t o have e l e c t r o d e s o u t s i d e o f t h e t h r e e t a r g e t a r e a s were n o t i n c l u d e d i n t h e s t a t i s t i c a l a n a l y s i s . E l e c t r o d e p l a c e m e n t s o f t h e r e m a i n i n g 61 r a t s a r e shown i n F i g . 1. T a s t e A v e r s i o n . F i g . 2 p r e s e n t s f l u i d c o n s u m p t i o n f o r t h e ABL (n=14), CD (n=9), SNC (n=9), and UNOP (n=10) d u r i n g t h e f i v e s a c c h a r i n t e s t s (days 7, 9, 11, 13, and 1 5 ) , as w e l l as w a t e r i n t a k e on t h e a l t e r n a t e days ( 6 , 8, 10, 12, and 14) o f t h e e x p e r i m e n t . A l t h o u g h t h e S A C - C n t l group was n o t i n c l u d e d i n t h e o r i g i n a l d e s i g n o f t h i s e x p e r i m e n t , d a t a from t h i s group a r e i n c l u d e d i n F i g . 2 f o r t h e purpose o f c o m p a r i s o n . As may be see n , t h e s e a n i m a l s d i s p l a y e d n e o p h o b i a on t h e f i r s t e x p o s u r e t o s a c c h a r i n , b u t g r e a t l y i n c r e a s e d t h e i r i n t a k e on subsequent t e s t s . There were s l i g h t d i f f e r e n c e s i n wa t e r i n t a k e w h i c h were a l s o r e f l e c t e d i n i n i t i a l s a c c h a r i n c o n s u m p t i o n o f the f o u r o r i g i n a l t r e a t m e n t g r o u p s . To a d j u s t f o r t h e s e i n i t i a l d i f f e r e n c e s , t h e s a c c h a r i n i n t a k e s o f each a n i m a l d u r i n g t h e r e t e n t i o n and e x t i n c t i o n t e s t s were e x p r e s s e d as p e r c e n t a g e s o f t h e p r e - L i C l s a c c h a r i n i n t a k e i n t h e condi-r tf-ionmngssession. The means o f t h e s e p e r c e n t a g e s c o r e s a r e shown i n F i g . 3. A r e p e a t e d measures a n a l y s i s o f v a r i a n c e (ANOVA) was a p p l i e d t o t h e r e t e n t i o n and e x t i n c t i o n p e r c e n t a g e s c o r e s o f t h e f o u r g r o u p s . The main e f f e c t o f t r e a t m e n t was s i g n i f i c a n t (F(3,38)=5.58, p < . 0 1 ) , as were t h e e f f e c t s o f t r i a l s (F(3,114)=88.65, p < .001) and t h e t r e a t m e n t - b y - t r i a l i n t e r a c t i o n (F(9,114)=6.84, p < . 0 0 1 ) . I n o r d e r t o d e t e r m i n e t h e d i f f e r e n c e s between t r e a t m e n t s on each t r i a l , an ANOVA f o r s i m p l e main e f f e c t s o f 17 F i g u r e 1. E l e c t r o d e p l a c e m e n t s i n t h e t h r e e s t i m u l a t i o n s i t e s o f E x p e r i m e n t I . P l a c e m e n t s from a n i m a l s i n t h e p a s s i v e a v o i d a n c e e x p e r i m e n t a r e .shown on t h e l e f t o f e a c h c o r o n a l s e c t i o n , and e l e c t r o d e s f r o m a n i m a l s i n t h e t a s t e a v e r s i o n e x p e r i m e n t a r e shown on t h e r i g h t . B r a i n s e c t i o n s were t a k e n from P e l l i g r i n o and Cushman ( 1 9 6 7 ) . CAUDATE P U T A M E N B A S O L A T E R A L AMYGDALA SUBSTANTIA NIGRA, ZONA COMPACTA 19 F i g u r e 2. Mean f l u i d i n t a k e o f w a t e r (upper p a n e l ) on t h e day p r e c e d i n g t a s t e a v e r s i o n c o n d i t i o n i n g (Wl) and a t 48 h r i n t e r v a l s t h e r e -a f t e r (W2-W5), and s a c c h a r i n ( l o w e r p a n e l ) d u r i n g c o n d i t i o n i n g (Cond.), r e t e n t i o n ( R e t e n . ) , and t h r e e e x t i n c t i o n ( E x t . ) t e s t s o f E x p e r i m e n t I . The f o u r groups i n c l u d e d t h o s e s t i m u l a t e d i n t h e b a s o l a t e r a l n u c l e u s o f t h e amygdala ( A B L ) , c a u d a t e n u c l e u s (CD), • r. t h e s u b s t a n t i a n i g r a , zona compacta (SNC) and t h e u n o p e r a t e d c o n t r o l s (UNOP). Unpoisoned s a c c h a r i n c o n t r o l s ( S A C - C n t l ) f r o m a n o t h e r e x p e r i m e n t a r e i n c l u d e d h e r e f o r c o m p a r i s o n . 21 F i g u r e 3. E f f e c t of b r a i n s t i m u l a t i o n i n b a s o l a t e r a l n u c l e u s o f t h e amygdala (ABL) , c a u d a t e , o r s u b s t a n t i a n i g r a zona compacta (SNC), compared w i t h u n o p e r a t e d c o n t r o l s , on r e t e n t i o n and e x t i n c t i o n o f c o n d i t i o n e d t a s t e a v e r s i o n . S a c c h a r i n i n t a k e s a r e e x p r e s s e d as p e r c e n t a g e s o f t h e i n t a k e d u r i n g t h e c o n d i t i o n i n g s e s s i o n , p r i o r t o p o i s o n i n g w i t h l i t h i u m c h l o r i d e . P e r c e n t a g e of p r e - l i t h i u m s a c c h a r i n i n t a k e o o 01 o CO o o o ro o o zz 23 t r e a t m e n t was a p p l i e d i n d e p e n d e n t l y t o t h e d a t a o f e a c h o f t h e t e s t d a y s . The r e s u l t s o f t h e s e a n a l y s e s a r e summarized i n T a b l e 1. S i g n i f i c a n t t r e a t -ment e f f e c t s were o b s e r v e d on t h e r e t e n t i o n and f i r s t two e x t i n c t i o n t e s t s . F u r t h e r m o r e , when Duncan's New M u l t i p l e Range t e s t s f o r p a i r w i s e c o m p a r i s o n s were a p p l i e d t o t h e s e t e s t d a y s , t h e ABL group d i f f e r e d s i g n i f i c a n t l y f r o m each o f t h e o t h e r t r e a t m e n t groups (p < .05), e x c e p t f o r t h e CD group on t h e second e x t i n c t i o n t e s t . These o b s e r v a t i o n s show t h a t t h e ABL s t i m u l a t i o n s e v e r e l y a t t e n u a t e d t h e c o n d i t i o n e d a v e r s i o n t o s a c c h a r i n , r e l a t i v e t o unoper-a t e d c o n t r o l s , w h i l e t h e o t h e r two s t i m u l a t e d groups showed no s u c h e f f e c t . However,, t h e l e v e l o f i n t a k e i n t h e ABL group was s t i l l w e l l below t h a t o f t h e SACC-Cntl group on t h e " r e t e n t i o n " t e s t ( s ee F i g . 2 ) , i n d i c a t i n g t h a t some a v e r s i o n may have been a s s o c i a t e d w i t h t h e ABL s t i m u l a t i o n and t a s t e c u e s . Stepdown Shock A v o i d a n c e . Each o f t h e t h r e e t r a i n i n g measures and t h e r e t e n t i o n measure a r e summarized i n F i g . 4, f o r t h e ABL (n=13), CD (n=8), SNC (n=8) and UNOP (n=10) t r e a t m e n t s . Each measure was t e s t e d f o r t r e a t m e n t e f f e c t by an in d e p e n d e n t ANOVA. None o f t h e main e f f e c t s were s i g n i f i c a n t i n t h e t h r e e measures o f a c q u i s i t i o n . I n r e t e n t i o n , however t h e t r e a t m e n t e f f e c t was s i g n i f i c a n t (F(3,35)=12.03, p < . 0 1 ) . Duncan:,'s t e s t showed t h a t t h e ABL, CD, and SNC groups a l l d i f f e r e d f rom UNOP, b u t n o t fr o m each o t h e r (p< .05). Hence, r e t e n t i o n o f t h e stepdown a v o i d a n c e r e s p o n s e was d i s r u p t e d by s t i m u l a t i o n a p p l i e d t o each o f t h e t h r e e s i t e s . The r e c o r d i n g s made from t h e ABL a f t e r t e s t i n g showed no e v i d e n c e o f a f t e r d i s c h a r g e a c t i v i t y , even when t h e i n t e n s i t y was i n c r e a s e d t o 30 uA. 24 TABLE 1 T a s t e A v e r s i o n P e r c e n t a g e S c o r e s , Means (+Standard E r r o r s ) R e t e n t i o n E x t i n c t i o n 1 E x t i n c t i o n 2 E x t i n c t i o n 3 ABL lO 6 . 5 ( + 2 0 O 3 ) a b c i 1 1 2 7 . 8 ( + 2 4 . 7 ) a b c 137.9(+16.4)ac 137.4(+15.1) CD 37.4(+7.8) 75.7(+14.3) 105.8(+13.1) 108.7(+17.0) SNC 28.7(+4.5) 47.9(+12.6) 87.4(+8.1) 121.0(+14.8) UNOP 25.2(+4.2) 35.5(+5.2) 81.9(+6.2) 127.4(+7.4) ANOVA 2 F(3,38)=8.48 F(3,38)=9.79 F(3,38)=4.21 F(3,38)=0.72 ( p < . 0 0 1 ) ( p < . 0 0 1 ) ( p < . 0 5 ) (p >.05) 1 R e s u l t s o f t h e Duncan's t e s t s a r e i n d i c a t e d by t h e l e t t e r s : a, d i f f e r e n t f rom UNOP, j ) , d i f f e r e n t f r o m CD, and c, d i f f e r e n t from SNC. 2 F v a l u e s a r e computed i n d e p e n d e n t l y f o r each o f t h e f o u r t e s t s . 25 F i g u r e 4. E f f e c t of b r a i n s t i m u l a t i o n i n t h e b a s o l a t e r a l n u c l e u s of t h e amygdala (ABL ) , c a u d a t e n u c l e u s (CD), and s u b s t a n t i a n i g r a zona compacta (SNC), compared w i t h u n o p e r a t e d c o n t r o l s ( C n t l ) , on A. number of d e s c e n t s , B. t i m e of c r i t e r i o n , and C. l a t e n c y t o f i r s t d e s c e n t , d u r i n g a c q u i s i t i o n o f stepdown p a s s i v e a v o i d a n c e . R e t e n t i o n s c o r e s a r e measured as l a t e n c y t o f i r s t d e s c e n t d u r i n g a r e t e s t 24 h r a f t e r a c q u i s i t i o n . S t a n d a r d e r r o r s a r e i n d i c a t e d w i t h each mean. A s t e r i s k s (*) i n d i c a t e s i g n i f i c a n t d i f f e r e n c e s ( p < .05, Duncan's M u l t i p l e Range t e s t ) f r o m u n o p e r a t e d c o n t r o l a n i m a l s ( C n t l ) . C n t l ABL CD S N C A . T r a i n i n g : D e s c e n t s Cnt l ABL CD S N C B. T r a i n i n g ; C r i t e r i o n Cnt l ABL CD S N C C. T r a i n i n g : L a t e n c y Cnt l ABL CD SNC D. R e t e n t i o n : L a t e n c y 27 D i s c u s s i o n These d a t a i n d i c a t e t h a t r e t e n t i o n of t h i s s hock a v o i d a n c e r e s p o n s e may be d i s r u p t e d by a p p l y i n g e l e c t r i c a l s t i m u l a t i o n t o t h e ABL, CD, o r SNC, t hus c o n f i r m i n g p r e v i o u s e x p e r i m e n t s ( G o l d ' _ e t ' a l . , 1973; F i b i g e r and P h i l l i p s , 1976; R o u t t e n b e r g and Holzman, 1973). On t h e o t h e r hand, r e t e n t i o n of t h e s a c c h a r i n t a s t e a v e r s i o n was d i s r u p t e d o n l y by s t i m u l a t i o n of t h e ABL. These o b s e r v a t i o n s may be i n t e r p r e t e d as f u r t h e r e v i d e n c e t h a t t h e n e u r a l c o r r e l a t e s of t h e two t a s k s may be d i f f e r e n t i a t e d by t h e p r e s e n t b r a i n s t i m u l a t i o n t e c h -n i q u e . The r e s u l t s o b t a i n e d w i t h ABL s t i m u l a t i o n do n o t e n t i r e l y c o n f i r m an e a r l i e r s t u d y by B resnehan and R o u t t e n b e r g ( 1 9 7 2 ) , These a u t h o r s r e p o r t e d t h a t r e t e n t i o n of t h e stepdown shock a v o i d a n c e r e s p o n s e was d i s r u p t e d by s t i m u l a t i o n a p p l i e d t o t h e m e d i a l b u t n o t b a s o l a t e r a l amygdala. The p r e s e n t r e s u l t s c l e a r l y showed impairment a f t e r ABL s t i m u l a t i o n . I t was assumed t h a t t h e s t i m u l a t i o n p a r a m e t e r s employed i n t h i s e x p e r i m e n t would n o t i n d u c e s e i z u r e s i n t h e amygdala ( c f . , Goddard, 1972; L i d s k y jet a l . , 1970). E l e c t r o g r a p h i c r e c o r d i n g s made a t t h e end o f t h e e x p e r -iment c o n f i r m e d t h a t t h i s was t h e c a s e : t h e r e was no e v i d e n c e of a f t e r d i s -c h a r g e a c t i v i t y d u r i n g t h e 10 min p e r i o d o f i n t e r m i t t e n t s t i m u l a t i o n o r f o r 5 min a f t e r w a r d s , even when t h e i n t e n s i t y was i n c r e a s e d f r o m 10 uA t o 30 uA. These o b s e r v a t i o n s c o n f i r m e d e a r l i e r r e p o r t s ( G o l d et: a l . , 1977; K e s n e r e t a l . , 1975) t h a t s e i z u r e a c t i v i t y i s n o t o b s e r v e d i n t h e amygdala a t s u c h low i n t e n -s i t i e s . The d i s r u p t i v e e f f e c t s of a m y g a l o i d s t i m u l a t i o n on d i f f e r e n t l e a r n i n g t a s k s i n v o l v i n g a v a r i e t y of s e n s o r y i n p u t s i s n o t s u r p r i s i n g i n v i e w of Kaada's (1972) r e v i e w o f t h e a n a t o m i c a l c o n n e c t i o n s o f t h e amygdala. I n a d d i t i o n t o t h e o l f a c t o r y p r o j e c t i o n (Cowan, Raisman, and P o w e l l , 1 9 65), the amygdala r e c e i v e s i n p u t s from t h e s omatosensory system (Wendt and A l b e - F e s s a r d , 28 1962) and t h e t a s t e system, r e c e n t l y c o n f i r m e d by N o r g r e n ( 1 9 7 6 ) , However, t h e p r e s e n t d a t a do n o t s p e c i f y what a s p e c t of memory f o r m a t i o n ( i f any) was m o d i f i e d by l o c a l i z e d a m y g d a l o i d s t i m u l a t i o n . F o r example, e l e c t r i c a l s t i m u l a t i o n a p p l i e d d u r i n g t a s t e a v e r s i o n c o n d i t i o n i n g m i g h t a f f e c t t h e s e n s a -t i o n of t h e s a c c h a r i n t a s t e o r t h e p e r c e p t i o n o f i t s n o v e l t y . A l t e r n a t i v e l y , t h e s t i m u l a t i o n may have i m p a r l e d t h e a s s o c i a t i o n o f t a s t e and i l l n e s s o r t h e c o n s o l i d a t i o n o f t h a t e x p e r i e n c e ( K e s n e r , 1 9 7 7 ) . I n o r d e r t o f a c t o r out t h e c o n t r i b u t i o n o f a g i v e n n e u r a l s t r u c t u r e t o i n f o r m a t i o n p r o c e s s i n g i n v o l v e d i n t h e a c q u i s i t i o n and r e t e n t i o n o f a newly l e a r n e d r e s p o n s e , K e s n e r and W i l b u r n (1974) have s u g g e s t e d t h a t b r a i n s t i m u l a t i o n be a p p l i e d t o t h e s t r u c t u r e i n q u e s t i o n i n a s y s t e m a t i c a l l y v a r i e d sequence. The f o l l o w i n g e x p e r i m e n t a p p l i e d t h i s a p p r o a c h t o t h e p r o b l e m o f ABL s t i m u l a t i o n and CTA. 29 EXPERIMENT I I . TASTE AVERSION WITH AMYGDALOID STIMULATION DURING VARIOUS PHASES OF CONDITIONING AND RETENTION T h i s e x p e r i m e n t was d e s i g n e d t o e x p l o r e i n g r e a t e r d e t a i l t h e a p p a r e n t d i s r u p t i o n o f t a s t e a v e r s i o n c o n d i t i o n i n g by l o w - i n t e n s i t y s t i m u l a t i o n o f t h e ABL. S t i m u l a t i o n was a p p l i e d t o t h r e e groups of r a t s d u r i n g d i f f e r e n t phases o f c o n d i t i o n i n g t o o b s e r v e t h e e f f e c t s on t h e a c q u i s i t i o n o f t h e c o n d i t i o n e d a v e r s i o n t o s a c c h a r i n . Two o t h e r groups were s t i m u l a t e d d u r i n g t h e r e t e n t i o n t e s t o r d u r i n g b o t h t h e c o n d i t i o n i n g and t h e r e t e n t i o n s e s s i o n s t o c o n t r o l f o r r e t r i e v a l d e f i c i t s and ESB-induced s t a t e - d e p e n d e n c y . (Kesner and W i l b u r n , 1974; O v e r t o n , 1974). A l s o , two u n s t i m u l a t e d g r o u p s , c o n s i s t i n g o f i m p l a n t e d and u n o p e r a t e d s u b j e c t s , were i n c l u d e d t o c o n t r o l f o r t h e e f f e c t s o f c h r o n i c e l e c t r o d e i m p l a n t a t i o n , w h i c h has been shown i n some i n s t a n c e s t o i n f l u e n c e l e a r n i n g and memory ( H e r z , M a r s h a l l , and Peeke, 1974; S a n t o s - A n d e r s o n and R o u t t e n b e r g , 1976). Method S u b j e c t s and S u r g e r y . S i x t y - t h r e e male r a t s werehhoused and f e d as d e s c r i b e d i n t h e G e n e r a l Method. E l e c t r o d e s (0.125 mm) were i m p l a n t e d i n 56 a n i m a l s , u s i n g t h e same p r o c e d u r e and c o o r d i n a t e s f o r t h e ABL as d e s c r i b e d i n t h e G e n e r a l Method s e c t i o n . The r e m a i n i n g s e v e n r a t s s e r v e d as u n o p e r a t e d c o n t r o l s (UNOP). A p p a r a t u s . T e s t i n g chambers, s t i m u l a t o r s , s a c c h a r . i n a c o n c e n t r a t i o n , and l i t h i u m dosage were t h e same as d e s c r i b e d . P r o c e d u r e . R e c o v e r y f r o m s u r g e r y and h a b i t u a t i o n t o w a t e r d e p r i v a t i o n were a r r a n g e d as b e f o r e . A f t e r 6 days of h a b i t u a t i o n , e ach i m p l a n t e d s u b j e c t was a s s i g n e d t o one of t h e s i x t r e a t m e n t g r o u p s . S a c c h a r i n a v e r s i o n c o n d i -t i o n i n g f o l l o w e d t h e p r o c e d u r e d e s c r i b e d i n t h e G e n e r a l Method, w i t h t h e 30 e x c e p t i o n o f t h e ESB a p p l i c a t i o n . I n t h e c o n d i t i o n i n g s e s s i o n , t h e 0.2% s a c c h a r i n s o l u t i o n was p r e s e n t e d f o r 10 m i n , t h e n w i t h d r a w n . A f t e r t h i s , a l l s u b j e c t s r emained i n t h e t e s t i n g chambers f o r 10 m i n . Then each was removed, g i v e n t h e a p p r o p r i a t e l i t h i u m i n j e c t i o n , and i m m e d i a t e l y r e t u r n e d t o t h e a p p r o -p r i a t e chamber f o r 10 m i n . C a r e was t a k e n t o e n s u r e t h a t a l l s u b j e c t s were exposed t o t h e t e s t chambers f o r t h e same amount of t i m e , r e g a r d l e s s of t r e a t m e n t c o n d i t i o n . Water was p r e s e n t e d f o r 10 m i n , 24 h r l a t e r s , and s a c c h -a r i n i n t a k e was measured d u r i n g a 10-min t e s t 48 h r a f t e r c o n d i t i o n i n g . As no e x t i n c t i o n t e s t s were g i v e n a f t e r t h i s r e t e n t i o n t e s t , a s i n g l e measure of s a c c h a r i n a v e r s i o n was computed f o r e ach s u b j e c t . T h i s r e t e n t i o n s c o r e e x p r e s s e d s a c c h a r i n i n t a k e i n t h e 48-hr r e t e n t i o n t e s t as a p r e c e n t a g e o f the i n t a k e d u r i n g t h e c o n d i t i o n i n g s e s s i o n , p r i o r t o l i t h i u m p o i s o n i n g . I n t r a c r a n i a l s t i m u l a t i o n was a p p l i e d t o 46 o f t h e i m p l a n t e d s u b j e c t s under f i v e s t i m u l a t i o n c o n d i t i o n s , as f o l l o w s : (1) SACC group (n=10) was s t i m u l a t e d f o r 10 min, d u r i n g s a c c h a r i n p r e s e n t a t i o n i n t h e c o n d i t i o n i n g s e s s -i o n , (2) INTERVAL group (n=9) was s t i m u l a t e d d u r i n g t h e 10-min i n t e r v a l b e t -ween s a c c h a r i n d r i n k i n g and l i t h i u m i n j e c t i o n , (3) L i C l group (n=9) was s t i m u l a t e d f o r H Q m-in<, h - i m m e d i a t e l y t a f t e r . f h e t h i C l i ' i h j e c t i o n , a t i m e t h a t would c o i n c i d e w i t h t h e o n s e t of i l l n e s s (Nachman, 1970), (4) RETEST group (n=9) was s t i m u l a t e d d u r i n g s a c c h a r i n p r e s e n t a t i o n i n t h e 48-hr r e t e s t , and (5) SAC+RET group (n=9) was s t i m u l a t e d d u r i n g s a c c h a r i n p r e s e n t a t i o n i n t h e c o n d i t i o n i n g s e s s i o n and a g a i n f o r 10 min i n t h e 48-hr r e t e n t i o n t e s t . As b e f o r e , s t i m u l a -t i o n was 60 Hz, AC, i n t r a i n s o f 3-sec 'on', 6-sec ' o f f . The i n t e n s i t y was i n i t i a l l y s e t a t 10 uA f o r a l l s t i m u l a t e d s u b j e c t s . As i n E x p e r i m e n t I , i f t h i s c u r r e n t i n h i b i t e d d r i n k i n g i n t h o s e i n d i v i d u a l s s t i m u l a t e d d u r i n g t h e i n i t i a l s a c c h a r i n p r e s e n t a t i o n ( i . e _ . , t h e SACC, and SAC+RET g r o u p s ) , t h e n t h e i n t e n s i t y was r e d u c e d t o a l e v e l a t w h i c h d r i n k i n g resumed. One a n i m a l t h a t d r a n k an a b n o r m a l l y s m a l l amount was dropped from t h e SACC gr o u p . F o r r a t s i n 31 t h e SAC+RET group, t h e i n t e n s i t i e s were d e t e r m i n e d 2 days b e f o r e c o n d i t i o n -i n g by a p p l y i n g s t i m u l a t i o n d u r i n g w a t e r p r e s e n t a t i o n . The r e s u l t i n g mean i n t e n s i t i e s and r a n g e s were: SACC, 5.0 uA (2-10 u A ) ; RETEST, 5.9 uA (5-9 u A ) ; and SAC+RET, 4.7 uA (2-10 u A ) . The UNOP and i m p l a n t e d (IMPLANT, n=10) c o n t r o l g roups r e c e i v e d no s t i m u l a t i o n d u r i n g c o n d i t i o n i n g o r r e t e n t i o n t e s t i n g . F our a n i m a l s f a i l e d t o c o m p l e t e t h e e x p e r i m e n t : one d e v e l o p e d an i n n e r e a r i n f e c t i o n , one d i e d d u r i n g h a b i t u a t i o n , and two l o s t t h e i r e l e c t r o d e a s s e m b l i e s . A t t h e end of t h e e x p e r i m e n t , t h e h i s t o l o g i c a l a n a l y s i s o f t h e r e m a i n i n g i m p l a n t e d a n i m a l s was c o n d u c t e d as d e s c r i b e d i n t h e G e n e r a l Method. R e s u l t s H i s t o l o g y . F i g . 5 shows t h e d i s t r i b u t i o n o f e l e c t r o d e t i p p l a c e m e n t s f o r t h e 47 i m p l a n t e d s u b j e c t s j u d g e d t o be i n o r on t h e p e r i m e t e r o f t h e ABL: SACC !(n=9), INTERVAL (n=8), L i C l (n=8), RETEST (n=8), SAC+RET (n=7), and IMPLANT, (n=7). O n l y t h o s e s u b j e c t s w i t h c o n f i r m e d e l e c t r o d e p l a c e m e n t s were i n c l u d e d i n t h e f o l l o w i n g s t a t i s t i c a l a n a l y s i s . P l a c e m e n t s ( i n d i c a t e d by open symbols) o u t s i d e o f t h e t a r g e t a r e a a l s o a r e shown i n t h e f i g u r e . T a s t e A v e r s i o n . The means and s t a n d a r d e r r o r s o f t h e r e t e n t i o n s c o r e s f o r t h e seven t r e a t m e n t groups a r e shown i n F i g . 6. The main e f f e c t f o r t r e a t -ment was s i g n i f i c a n t (F(6,47)=12.18, p <.001). Duncan's New M u l t i p l e Range t e s t f o r p a i r w i s e c o m p a r i s o n s r e v e a l e d t h a t t h e means of t h e SACC, INTERVAL, and L i C l groups were g r e a t e r t h a n t h o s e o f t h e UNOP, IMPLANT, RETEST, and SAC+RET g r o u p s . A l s o , t h e mean of t h e INTERVAL group was l e s s t h a n t h a t o f the SACC group. These o b s e r v a t i o n s s u g g e s t t h a t a m y g d a l o i d s t i m u l a t i o n a p p l i e d d u r i n g t h e s a c c h a r i n p r e s e n t a t i o n , d u r i n g t h e i n t e r s t i m u l u s i n t e r v a l , o r d u r i n g t h e o n s e t o f l i t h i u m i i l l n e s s a t t e n u a t e d t h e f o r m a t i o n o f a c o n d i t i o n e d a v e r s i o n t o s a c c h a r i n , r e l a t i v e t o u n o p e r a t e d and i m p l a n t e d c o n t r o l s . A n i m a l s s t i m u -l a t e d d u r i n g s a c c h a r i n p r e s e n t a t i o n i n t h e r e t e n t i o n t e s t (RETEST), o r d u r i n g 32 F i g u r e 5. E l e c t r o d e p l a c e m e n t s from t h e d i f f e r e n t groups t e s t e d i n E x p e r i m e n t t I I . The t r e a t m e n t s a r e as f o l l o w s : (1) SACC, r a t s s t i m u l a t e d d u r - . i n g c o n s u m p t i o n of s a c c h a r i n s o l u t i o n d u r i n g c o n d i t i o n i n g , (2) INTERVAL, r a t s s t i m u l a t e d between s a c c h a r i n p r e s e n t a t i o n and L i C l i n j e c t i o n , (3) L i C l , r a t s s t i m u l a t e d i m m e d i a t e l y a f t e r t h e L i C l i n j e c t i o n , (4) RETEST, r a t s s t i m u l a t e d d u r i n g r e t e s t , 48 h r a f t e r t h e p a i r i n g o f s a c c h a r i n w i t h L i C l , (5) SAC+RET, r a t s s t i m u l a t e d w h i l e d r i n k i n g s a c c h a r i n d u r i n g c o n d i t i o n i n g and r e t e n t i o n , and (.6) i m p l a n t e d c o n t r o l s n o t s t i m u l a t e d d u r i n g t h e p r o c e d u r e . The d a t a o f a n i m a l s w i t h p l a c e m e n t s o u t s i d e t h e ABL (open symbols) a r e n o t i n c l u d e d i n t h e a n a l y s i s . B r a i n s e c t i o n s were t a k e n f r o m P e l l e g r i n o and Cushman (1 9 6 7 ) . 34 F i g u r e 6. S a c c h a r i n i n t a k e s d u r i n g t h e r e t e n t i o n t e s t , e x p r e s s e d as p e r c e n -t a g e of t h e i n t a k e s d u r i n g c o n d i t i o n i n g , b e f o r e l i t h i u m p o i s o n i n g . V a l u e s shown a r e means w i t h s t a n d a r d e r r o r s ; a s t e r i s k s (*) i n d i c a t e s i g n i f i c a n t d i f f e r e n c e s from UNOP c o n t r o l s CP<.05, Duncan's M u l t i p l e Range TSsf)!. P E R C E N T A G E OF P R E - L i C I I N T A K E to o 4^. O 0) O 00 O O O ro o > O o Z a o z > o o m 33 < > O 33 m H m 3J Ui m+> H O c z o "0 2 > z 3 c o 3 H 36 s a c c h a r i n p r e s e n t a t i o n b o t h i n c o n d i t i o n i n g and i n r e t e n t i o n s e s s i o n s (SAC+RET) t s t i l l showed s u p p r e s s i o n of s a c c h a r i n i n t a k e , s i m i l a r t o t h a t o f u n s t i m u l a t e d c o n t r o l s . The a v e r s i o n appeared t o have been l e a r n e d and r e t r i e v e d i n t h e p r e -sence o f a m y g d a l o i d s t i m u l a t i o n . F i n a l l y , s u r g e r y and i m p l a n t a t i o n had no o b s e r v a b l e e f f e c t on t h e p r e s e n t CTA, and t h e IMPLANT group showed no s i g -n i f i c a n t d i f f e r e n c e from t h e UNOP group. These o b s e r v a t i o n s a r e c o n f i r m e d by e x a m i n i n g t h e mean w a t e r and s a c c h a r i n i n t a k e s , p r e s e n t e d i n T a b l e 2. The UNOP group showed no r e d u c e d i n t a k e when s a c c h a r i n was p r e s e n t e d on t h e c o n d i t i o n i n g day, r e l a t i v e t o t h e water i n t a k e on t h e p r e v i o u s day. The o t h e r groups showed o n l y a m i l d neo-p h o b i a t o t h e s a c c h a r i n s o l u t i o n , whether p r e s e n t e d a l o n e (INTERVAL, L i C l , RETEST, and IMPLANT t r e a t m e n t s ) o r c o n c u r r e n t l y w i t h a m y g d a l o i d s t i m u l a t i o n (SACC and SAC+RET t r e a t m e n t s ) . I n c o n t r a s t , t h e S A C - C n t l group (see F i g . 2) showed a s t r o n g n e o p h o b i a when f i r s t p r e s e n t e d w i t h t h e s a c c h a r i n s o l u t i o n , as t h e i r i n t a k e d e c r e a s e d by 6.4 m l . S u b j e c t s s t i m u l a t e d d u r i n g t h e s a c c h a r i n r e t e s t (RETEST and SAC+RET) were t e s t e d l a t e r on the same day, w i t h ESB a p p l i e d f o r 10 min, w h i l e w a t e r was a v a i l a b l e . The mean i n t a k e s o f t h e s e two groups i s shown i n T a b l e 2 i n the "W + S t " column. The i n t a k e o f t h e RETEST group i n t h i s p o s t hoc t e s t was s i m i l a r t o t h e i n t a k e i n t h e second w a t e r t e s t . T h i s s u g g e s t e d t h a t t h e redu c e d i n t a k e seen i n t h e s a c c h a r i n r e t e s t was due t o an a v e r s i o n t o s a c -c h a r i n , n o t t o a g e n e r a l decrement i n f l u i d i n t a k e , p r o duced by t h e a v e r s i v e -n ess o f c o n c u r r e n t ESB. A l t h o u g h t h e i n t a k e o f t h e SAC+RET group was r e d u c e d by 37%, r e l a t i v e t o t h e second w a t e r t e s t , i t was n o t low enough t o a c c o u n t e n t i r e l y f o r t h e 75% s u p p r e s s i o n ('.'aversion") seen i n t h e s a c c h a r i n r e t e s t . The p o s s i b i l i t y r e m a i n s , however, t h a t ESB i n h i b i t e d d r i n k i n g i n t h i s g r o u p , w h i c h may a c c o u n t i n p a r t f o r t h e " a v e r s i o n " o b s e r v e d . TABLE 2. MEAN (+ STANDARD ERROR) WATER AND SACCHARIN INTAKE IN EXPERIMENT I I SACC (9) 1 INTERVAL (8) L i C l (8) RETEST (8) SAC+RET (7) UNOP (7) IMPLANT (7) Water 12.6(+1.1) 12.9(+1.0) 13.6(+0.5) 12.60+O.6) 11.9(+1.1) 11.5(+1.3) 14.8(+0.3) C o n d i t i o n i n g 10.7(+0.9) 11.8(+1.3) 11.4(+1.0) 10.7(+0.9) 10.0(+1.3) 12.3(+0.7) 13.4(+1.3) Water 12.3C+0.9) 1 2 . K + 1 . 0 ) 11.8C+0.8) 8 . K + 1 . 7 ) 9.6C+1.8) 12.4(+1.1) 13.6(+0.5) R e t e n t i o n 9 . 9 ( + l . l ) 8.0(+1.2) 9.4C+0.8) 2.7(+0.8) 2.4(+0.4) 3.4(+0.8) 4.0(+1.0) 2 Water + S t i m 9.3(+0_.7) 6.0(+1.5) "*-See t e x t f o r e x p l a n a t i o n o f t r e a t m e n t g r o u p s . ^Water i n t a k e i n t h e p r e s e n c e o f ABL s t i m u l a t i o n , t e s t e d l a t e r i n t h e same day as t h e r e t e n t i o n t e s t . to 38 D i s c u s s i o n The r e s u l t o f t h e SACC, INTERVAL, and L i C l g roups s u p p o r t e d t h e f i n d i n g s of E x p e r i m e n t I . The a v e r s i o n t o s a c c h a r i n d u r i n g t h e r e t e n t i o n t e s t appeared t o be i m p a i r e d by t h e a d m i n i s t r a t i o n o f a m y g d a l o i d s t i m u l a t i o n a t e a c h o f t h e s e d i f f e r e n t phases o f t h e c o n d i t i o n i n g p r o c e d u r e . These d i s -r u p t i o n s ; , d i d n o t appear t o be due t o c h r o n i c e l e c t r o d e i m p l a n t a t i o n , as t h e IMPLANT group showed a s a c c h a r i n a v e r s i o n as g r e a t as t h a t o f t h e UNOP c o n t r o l s . The INTERVAL t r e a t m e n t p roduced a s m a l l e r d e f i c i t t h a n t h e SACC t r e a t m e n t , as the mean r e t e n t i o n s c o r e o f t h e s e s u b j e c t s was i n t e r m e d i a t e between t h a t o f the SACC and UNOP g r o u p s . These d a t a a g r e e i n g e n e r a l w i t h t h e r e p o r t o f Kesn e r e t a l . (1975) t o t h e e x t e n t t h a t a m y g d a l o i d s t i m u l a t i o n a p p l i e d a f t e r t h e s a c c h a r i n cue and b e f o r e t h e i l l n e s s cue i s l e s s d i s r u p t i v e . The above i m p a i r m e n t s i n CTA m i g h t be e x p l a i n e d i n terms o f t h e model o f memory pro p o s e d by K e s n e r ( 1 9 7 7 ) . A l t h o u g h a m y g d a l o i d s t i m u l a t i o n may have i n t e r r u p t e d a s i n g l e a s p e c t o f memory p r o c e s s i n g i n t h e f i r s t t h r e e t r e a t m e n t g r o u p s , i t a l s o i s p o s s i b l e t h a t ESB i n f l u e n c e d d i f f e r e n t p r o c e s s e s i n each o f t h e t h r e e g r o u p s . F o r example, s t i m u l a t i o n a p p l i e d d u r i n g t h e p r e s e n t a t i o n o f t h e s a c c h a r i n s o l u t i o n may have m o d i f i e d t h e p e r c e p t i o n o f t h e t a s t e cue o r t h e i n c o r p o r a t i o n o f t h a t cue i n t o memory. On t h e o t h e r hand, s t i m u l a t i o n d u r i n g t h e i n t e r s t i m u l u s i n t e r v a l may have i n t e r f e r e d w i t h r e -h e a r s a l o f t h a t cue, t r a n s f e r t o l o n g - t e r m memory, o r w i t h some o t h e r p r o c e s s n e c e s s a r y f o r t h e a s s o c i a t i o n o f t a s t e and i l l n e s s . F i n a l l y , s t i m u l a t i o n d u r i n g t h e o n s e t o f i l l n e s s a l s o may have i n t e r f e r e d w i t h r e h e a r s a l o f t h e t a s t e cue, o r i t may have a f f e c t e d t h e i n i t i a l a v e r s i v e n e s s o f l i t h i u m t o x i -c o s i s , a l t h o u g h t h i s l a t t e r p o s s i b i l i t y i s u n l i k e l y i n l i g h t o f t h e c o n t r o l s r u n by K e s n e r e t a l . (1975) f o r s u c h an e f f e c t . By r e s t r i c t i n g t h e a n a l y s i s t o t h e above d a t a , one mi g h t c o n c l u d e t h a t t h e e f f e c t o f a m y g d a l o i d s t i m u l a t i o n was p r i m a r i l y t o i n h i b i t some a s p e c t o f 39 memory p r o c e s s i n g . That i s , ESB may have d i s r u p t e d t h e a s s o c i a t i o n o f t a s t e and i l l n e s s , p o s s i b l y by i n h i b i t i n g a p r o c e s s s u c h as c o n s o l i d a t i o n o f memory of t h e s a c c h a r i n t a s t e o r of t h e t a s t e - i l l n e s s e x p e r i e n c e . The o b s e r v a t i o n t h a t s u b j e c t s i n t h e RETEST group showed an a v e r s i o n s u g g e s t s t h a t a m y g d a l o i d s t i m u l a t i o n p e r se does n o t n e c e s s a r i l y d i s r u p t t h e r e t r i e v a l o f t h e t a s t e -i l l n e s s a s s o c i a t i o n , t h e r e b y r u l i n g o u t d i s r u p t i o n o f t h i s p r o c e s s as an e x p l a n a t i o n o f t h e a p p a r e n t memory d e f i c i t . The o b s e r v a t i o n t h a t t h e c o n -d i t i o n e d a v e r s i o n appeared t o be i n t a c t i n t h e SAC+RET group s u g g e s t s t h a t s t i m u l a t i o n d u r i n g t r a i n i n g a l o n e ( a t l e a s t i n t h e c a s e o f t h e SACC group) d i d n o t i n h i b i t t h e p r o c e s s o f memory c o n s o l i d a t i o n , as an a v e r s i o n was e v i d e n t when s t i m u l a t i o n was a p p l i e d d u r i n g b o t h c o n d i t i o n i n g and r e t e n t i o n t e s t s . I n t h e f i n a l a n a l y s i s , a t t e m p t s t o e x p l a i n t h e s e d a t a i n t t e r m s o f d i s r u p t i o n o f memory p r o c e s s e s appear i n a d e q u a t e . The r e s u l t s o f t h e SAC+RET group cannot be e x p l a i n e d i n terms o f d i s r u p t i o n o f memory, b u t t h e y may be i n t e r p r e t e d i n terms o f s t i m u l u s c o n t r o l ( M a c k i n t o s h , 1975). A c c o r d i n g t o t h i s h y p o t h e s i s , a m y g d a l o i d s t i m u l a t i o n would f u n c t i o n as a cue t h a t c o u l d be compounded w i t h t h e cue p r o v i d e d by t h e s a c c h a r i n f l a v o r . These two cues c o u l d form a s t i m u l u s compound t h a t would i n t u r n be a s s o c i a t e d w i t h t h e l i t h i u m i l l n e s s . I f t h i s were t h e c a s e , when t h e groups were r e t e s t e d 48 h r l a t e r , a s t r o n g a v e r s i o n s h o u l d o n l y be o b s e r v e d i f b o t h elements o f t h e s t i m u l u s compound were p r e s e n t . T h i s , i n f a c t , was t h e c a s e i n t h e SAC+RET c o n d i t i o n . No a v e r s i o n would be e x p e c t e d when t h e t a s t e cue, but n o t t h e ESB cue, was p r e s e n t i n t h e r e t e s t , as was o b s e r v e d i n t h e SACC group. The r e s u l t s o f t h e INTERVAL and L i C l t r e a t m e n t s can a l s o be i n t e r p r e t e d i n l i g h t o f s t i m u l u s c o n t r o l . I n b o t h o f t h e s e t r e a t m e n t s , t h e l a s t r e l e v a n t cue b e f o r e t h e o n s e t o f l i t h i u m i l l n e s s would have been t h e a m y g d a l o i d s t i m u l a t i o n . 40 I f t h e memory of s a c c h a r i n o r i t s a f t e r t a s t e had p e r s i s t e d d u r i n g t h i s p e r i o d , a compound s t i m u l u s composed o f ESB and t h e t a s t e cues c o u l d have been formed. As i n t h e SACC t r e a t m e n t group, when one element of t h e compound s t i m u l u s was a b s e n t i n t h e r e t e n t i o n t e s t , no a v e r s i o n would be o b s e r v e d . On l o g i c a l g r o u n d s , t h e r e s u l t of t h e RETEST group would appear t o be i n c o n s i s t e n t w i t h t h e s t i m u l u s c o n t r o l e x p l a n a t i o n o f how ESB i n f l u e n c e s CTA. T h i s e x p l a n a t i o n would p r e d i c t t h a t a n i m a l s w i t h an a v e r s i o n c o n d i t i o n e d t o t a s t e a l o n e s h o u l d show a s i g n i f i c a n t a t t e n u a t i o n o f t h e i r a v e r s i o n i f p r e -s e n t e d w i t h a n o v e l s t i m u l u s compound d u r i n g t h e r e t e s t . Such a p r e d i c t i o n f o l l o w s from t h e o r i g i n a l o b s e r v a t i o n t h a t a n i m a l s c o n d i t i o n e d t o a s t i m u l u s compount ( s a c c h a r i n p l u s ESB) showed an a t t e n u a t i o n o f t h e a v e r s i o n when p r e -s e n t e d w i t h t a s t e a l o n e on t h e r e t e n t i o n t r i a l . However, i t must be n o t e d t h a t t h i s p r e d i c t i o n assumes t h a t t h e e lements i n t h e compound a r e e q u a l l y s a l i e n t whether p r e s e n t e d b e f o r e o r a f t e r l i t h i u m p o i s o n i n g . T h i s i s n o t n e c e s s a r i l y t h e c a s e , as i t has been s u g g e s t e d t h a t t h e s a l i e n c e of t a s t e s t i m u l i may i n c r e a s e as a r e s u l t of t h e i r a s s o c i a t i o n w i t h i l l n e s s ( G a r c i a e t al. 1974). T h i s v i e w i s c o n s i s t e n t w i t h M a c k i n t o s h ' s (1975) i d e a t h a t t h e a s s o c i a t i v e s t r e n g t h o f one element i n a compound may i n c r e a s e when i t i s s e l e c t i v e l y r e i n f o r c e d . I n t h e RETEST group of E x p e r i m e n t I I , o n l y s a c c h a r i n was p a i r e d w i t h L i C l d u r i n g a c q u i s i t i o n , w h i l e b o t h ESB and s a c c h a r i n were p r e s e n t e d d u r i n g t h e r e t e n t i o n t r i a l . T h e r e f o r e , t h e s a l i e n c e of t h e t a s t e s t i m u l u s c o u l d have been g r e a t l y enhanced f o l l o w i n g i t s a s s o c i a t i o n w i t h i l l n e s s . T h i s p o s s i b i l i t y , however, r e q u i r e s f u r t h e r e x p e r i m e n t a l e x a m i n a t i o n . B e f o r e a c c e p t i n g t h e s t i m u l u s c o n t r o l h y p o t h e s i s , i t i s a l s o i m p o r t a n t to d e a l w i t h t h e p o s s i b i l i t y t h a t t h e a m y g d a l o i d s t i m u l a t i o n was i t s e l f a v e r s i v e . P r e s e n t a t i o n of a v e r s i v e ESB would be e x p e c t e d t o s u p p r e s s d r i n k i n g , t h e r e b y o b s c u r i n g t h e e f f e c t s of c o n d i t i o n i n g . To r u l e o u t t h i s p o s s i b i l i t y , t h e r e i n f o r c i n g p r o p e r t i e s o f ABL s t i m u l a t i o n were examined i n a 41 s e l f - s t i m u l a t i o n . t e s t . One week a f t e r t h e s a c c h a r i n r e t e s t , a b a r was made a v a i l a b l e i n each t e s t box. E a c h b a r p r e s s d e l i v e r e d a c u r r e n t o f t h e same d u r a t i o n (3 s e c ) and i n t e n s i t y (2-10 uA) employed i n t h e CTA e x p e r i m e n t . Four a n i m a l s i n each of t h e two groups (RETEST and SAC+RET) were t e s t e d i n 30-min s e s s i o n s f o r 2 days. F i v e o t h e r a n i m a l s ( w i t h CTA and ESB e x p e r i e n c e , but no p r e v i o u s s e l f - s t i m u l a t i o n t e s t s ) were p l a c e d i n t h e boxes w i t h t h e s t i m u l a t i n g c u r r e n t o f f . The mean o p e r a n t r a t e f o r t h e s e a n i m a l s on t h e 2nd day was 22.2 p r e s s e s i n 30 min ( r a n g e , 2-44 p r e s s e s ) . The mean s e l f -s t i m u l a t i o n r a t e s f o r t h e RETEST and SAC+RET groups on t h e second day were 72.5 (r a n g e , 15-125 p r e s s e s ) and 79.2 ( r a n g e , 49-104), r e s p e c t i v e l y . F u r t h e r m o r e , o n l y aone a n i m a l (15 p r e s s e s / 30 min) f a i l e d t o r e t u r n t o t h e b a r and p r e s s t h r o u g h o u t t h e second 30-min s e s s i o n . A l t h o u g h t h e s e l f - s t i m u l a t i o n r a t e s o f the o t h e r r a t s i n t h e two groups were low, t h e y s t r o n g l y s u g g e s t t h a t t h e a m y g d a l o i d s t i m u l a t i o n used i n t h e t a s t e a v e r s i o n e x p e r i m e n t was p o s i t i v e l y r e i n f o r c i n g , r a t h e r t h a n a v e r s i v e . P e r h a p s t h e s t r o n g e s t a l t e r n a t i v e t o t h e s t i m u l u s c o n t r o l h y p o t h e s i s i s an e x p l a n a t i o n based on s t a t e - d e p e n d e n t l e a r n i n g ( O v e r t o n , 1 9 7 4 ) . A l t h o u g h s t a t e dependency cannot be d i s c o u n t e d c o m p l e t e l y , t h e d a t a o f t h e RETEST group s u g g e s t t h a t i t i s u n l i k e l y t o p r o v i d e an e x p l a n a t i o n o f t h e p r e s e n t r e s u l t s . S p e c i f i c a l l y , a s t a t e - d e p e n d e n c y model p r e d i c t s t h a t a m y g d a l o i d s t i m u l a t i o n e s t a b l i s h e s a u n i q u e s t a t e o f b r a i n a c t i v a t i o n , such t h a t CTA would o n l y be d i s p l a y e d i f t h e same s t a t e were produced d u r i n g c o n d i t i o n i n g and r e t e n t i o n t e s t i n g . T h i s was t h e c a s e w i t h t h e SAC+RET group, and s u p p r e s s i o n o f d r i n k i n g (CTA) was o b s e r v e d . When ESB was a d m i n i s t e r e d o n l y d u r i n g c o n d i t i o n i n g (SACC, INTERVAL, and L i C l t r e a t m e n t s ) , t h e s u p p r e s s i o n o f d r i n k i n g was a t t e n u a t e d , r e l a t i v e t o u n s t i m u l a t e d c o n t r o l s , a f i n d i n g t h a t a l s o may be a t t r i b u t e d t o d i f f e r e n t s t a t e s i n a c q u i s i t i o n and r e t e n t i o n . C o n t r a r y t o t h e p r e d i c t i o n , however, a s u b s t a n t i a l s u p p r e s s i o n was o b s e r v e d when ESB was a p p l i e d o n l y 42 d u r i n g r e t e n t i o n , and n o t d u r i n g c o n d i t i o n i n g (RETEST t r e a t m e n t ) . A c c o r d i n g t o t h e s t a t e - d e p e n d e n c y h y p o t h e s i s , t h i s t r e a t m e n t s h o u l d have d i s r u p t e d t h e a v e r s i o n , because d i f f e r e n t s t a t e s were imposed on t h e a n i m a l s d u r i n g a c q u i s i -t i o n and r e t e n t i o n . The f a c t t h a t 75% s u p p r e s s i o n was o b s e r v e d i n t h e RETEST group g r e a t l y d i m i n i s h e s t h e a p p e a l o f t h e s t a t e - d e p e n d e n c y argument. I n summary, i t seems i n a p p r o p r i a t e t o e x p l a i n t h e d i s r u p t i o n o f s a c -c h a r i n a v e r s i o n , as seen i n E x p e r i m e n t I , as a g e n e r a l decrement i n memory f o r m a t i o n , o r as an i n s t a n c e o f s t a t e - d e p e n d e n t l e a r n i n g . The d a t a o f t h e s u b j e c t s s t i m u l a t e d d u r i n g b o t h r e t e n t i o n and c o n d i t i o n i n g t r i a l s ( t h e SAC+RET) g r o u p ) c l e a r l y show t h a t memory f o r m a t i o n and r e t r i e v a l may t a k e p l a c e i n t h e p r e s e n c e of a m y g d a l o i d s t i m u l a t i o n . D e f i c i t s i n t h e s u p p r e s s i o n o f s a c c h a r i n i n t a k e appear t o be a r e s u l t o f s t i m u l u s c o n t r o l . A c c o r d i n g t o t h i s m o del, l i t h i u m i l l n e s s was a s s o c i a t e d w i t h a s t i m u l u s compound, t a s t e p l u s ESB. When one element of t h e compound, ESB, was a b s e n t d u r i n g t h e r e t e n t i o n t e s t , t h e c o n d i t i o n e d a v e r s i o n was s i g n i f i c a n t l y i m p a i r e d . T h i s i n t e r p r e t a t i o n o f t h e p r e s e n t d a t a assumes t h a t a m y g d a l o i d s t i m u l a t i o n f u n c t i o n e d as a cue f o r l i t h i u m - i n d u c e d i l l n e s s , much as a n o v e l t a s t e i n t h e same s i t u a t i o n . The f o l l o w i n g e x p e r i m e n t was u n d e r t a k e n t o examine t h e p o s s i b i l i t y t h a t s u c h b r a i n s t i m u l a t i o n a l o n e m i g h t be a s s o c i a t e d w i t h L i C l i l l n e s s . 43 EXPERIMENT I I I . ELECTRICAL STIMULATION OF THE AMYGDALA AS A CONDITIONED STIMULUS FOR TASTE AVERSION The r e s u l t s o f E x p e r i m e n t I I s u g g e s t e d t h a t a m y g d a l o i d s t i m u l a t i o n may a c t as a cue o r c o n d i t i o n e d s t i m u l u s (CS) f o r l i t h i u m i l l n e s s . One way t o e x p l o r e such a p o s s i b i l i t y would be t o a p p l y a m y g d a l o i d s t i m u l a t i o n d u r i n g w a t e r d r i n k i n g and t o f o l l o w t h i s by a L i C l i n j e c t i o n . I f ESB does, i n f a c t , a c t as a cue f o r L i C l - i n d u c e d i l l n e s s i n such a par a d i g m , subsequent t e s t i n g s h o u l d r e v e a l a c o n d i t i o n e d a v e r s i o n t o " s t i m u l a t i o n - f l a v o r e d " w a t e r . The p r e s e n t e x p e r i m e n t was d e s i g n e d t o p a i r ESB and l i t h i u m i l l n e s s i n a s i t u a t i o n c omparable t o t h a t o f t h e p r e c e d i n g two e x p e r i m e n t s , and t o o b s e r v e any sub-sequent s u p p r e s s i o n o f w a t e r d r i n k i n g i n t h e p r e s e n c e o f a m y g d a l o i d s t i m u l a t i o n . A d d i t i o n a l groups were i n c l u d e d t o c o n t r o l f o r s e n s i t i z a t i o n and o t h e r non-s p e c i f i c e f f e c t s o f i m p l a n t a t i o n and i n t r a c r a n i a l s t i m u l a t i o n . As a c o n t r o l f o r t h e l o c u s - s p e c i f i c e f f e c t o f ABL s t i m u l a t i o n , groups r e c e i v i n g c a u d a t e s t i m u l a t i o n were a l s o i n c l u d e d i n t h e e x p e r i m e n t a l d e s i g n . Method S u b j e c t s and S u r g e r y . S e v e n t y male r a t s were housed and f e d as b e f o r e . I m p l a n t a t i o n f o l l o w e d t h e s t a n d a r d p r o c e d u r e , w i t h e l e c t r o d e s aimed a t t h e ABL (n=33) o r CD (n=30). The r e m a i n i n g s e v e n r a t s s e r v e d as u n o p e r a t e d c o n t r o l s . A p p a r a t u s . T e s t i n g chambers, s t i m u l a t o r s , c a r r y i n g b o x e s , s a c c h a r i n s o l u t i o n , and L i C l dosage were as d e s c r i b e d i n t h e G e n e r a l Method. P r o c e d u r e . H a b i t u a t i o n t o t h e d e p r i v a t i o n s c h e d u l e f o r 6 days f o l l o w e d t h e p r o c e d u r e p r e v i o u s l y d e s c r i b e d . On day 77i, i m p l a n t e d s u b j e c t s were d i v i d e d i n t o s i x t r e a t m e n t groups on t h e b a s i s o f w a t e r i n t a k e . The t h r e e ABL groups were d e n o t e d : ABL-Cue (n=12), A B L - S t i m (n=12), and ABL-Impl (n=9). The c a u d a t e 44 groups were denoted: CD-Cue (n=12), CD-Stim (n=10), and CD-Impl (n=S) . I n t h e c o n d i t i o n i n g s e s s i o n , t h e s a c c h a r i n s o l u t i o n was p r e s e n t e d t o t h e unoper-a t e d c o n t r o l s (SAC-Cue) f o r 10 m i n , t h e n w i t h d r a w n . Ten m i n u t e s l a t e r , each r a t was removed f r o m t h e t e s t chamber, i n j e c t e d w i t h t h e a p p r o p r i a t e dose o f L i C l (.15M, 20 m l / k g ) , and r e t u r n e d t o t h e home cage. T h i s c o n t r o l g r o u p , t e s t e d i n a s t a n d a r d CTA paradigm, was i n c o r p o r a t e d t o p r o v i d e a p a t t e r n o f f l u i d i n t a k e w i t h w h i c h t o compare t h e e f f e c t o f s u b s t i t u t i n g ESB as t h e CS. The i m p l a n t e d s u b j e c t s were p r e s e n t e d w i t h u n f l a v o r e d w a t e r i n t h e c o n d i t i o n i n g s e s s i o n . I n t r a c r a n i a l s t i m u l a t i o n (10 uA) was a p p l i e d t o r a t s i n t h e ABL-Cue and CD-Cue groups d u r i n g t h e 10-min d r i n k i n g p e r i o d . Ten m i n u t e s a f t e r t h e w a t e r was w i t h d r a w n , each s u b j e c t was i n j e c t e d w i t h t h e a p p r o p r i a t e L i C l dose and r e t u r n e d t o i t s home cage. As c o n t r o l s f o r t h e p o s s i b l e a v e r s i v e e f f e c t s o f E E S B , r a t s i n t h e A B L - S t i m and CD-Stim groups were a l s o s t i m u l a t e d d u r i n g t h e w a t e r p r e s e n t a t i o n , b u t i n j e c t e d w i t h i s o m o l a r s a l i n e (.15M N a C l , 20 ml/kg) i n s t e a d of L i C l . As i n E x p e r i m e n t I , i f t h e 10-uA c u r r e n t i n h i b i t e d d r i n k i n g , i t was r e d u c e d t o a l e v e l a t w h i c h d r i n k i n g resumed. The r e s u l t i n g mean c u r r e n t i n t e n s i t i e s - f o r t h e a n i m a l s t h a t com-p l e t e d t h e e x p e r i m e n t were ABL-Cue, 3.11 uA ( r a n g e , 2.5-5.0 uA) ; A B L - S t i m , 3.40 uA ( 2 . 5 - 6 . 0 ) ; CD-Cue, 8.33 uA (5.0-10.0 u A ) ; and CD-Stim, 8.57 uA (5.0-10.0 u A ) . As a c o n t r o l f o r t h e e f f e c t s o f e l e c t r o d e i m p l a n t a t i o n , two groups w i t h ABL o r CD e l e c t r o d e s were i n c l u d e d . The ABL-Impl and CD-Impl groups were p r e -s e n t e d w i t h w a t e r , but no i n t r a c r a n i a l s t i m u l a t i o n , d u r i n g t h e d r i n k i n g p e r i o d and i n j e c t e d w i t h t h e a p p r o p r i a t e L i C l dose a f t e r 10 m i n . Water ( w i t h o u t ESB) was p r e s e n t e d t o a l l r a t s on t h e day f o l l o w i n g t h e c o n d i t i o n i n g s e s s i o n (day 8) and on s u c c e s s i v e a l t e r n a t e days (10, 12, and 14) t o e n s u r e t h a t no g e n e r a l d r i n k i n g d e f i c i t had been produced by t h e L i C l 45 i n j e c t i o n . F l u i d i n t a k e was r e t e s t e d on day 9, 48 h r a f t e r t r a i n i n g , under t h e same c o n d i t i o n s as p r e v a i l e d f o r e a c h group d u r i n g c o n d i t i o n i n g . A l s o , t h r e e e x t i n c t i o n t e s t s were c a r r i e d o ut on days 11, 13, and 15. A t t h e end of t h e e x p e r i m e n t t h e h i s t o l o g i c a l a n a l y s i s o f a l l i m p l a n t e d a n i m a l s was condu c t e d as i n t h e G e n e r a l Method. R e s u l t s The d i s t r i b u t i o n o f e l e c t r o d e p l a c e m e n t s f o r 56 i m p l a n t e d r a t s i s p r e s e n t e d i n F i g . 7. Seven o t h e r i m p l a n t e d a n i m a l s had been dropped f r o m t h e e x p e r i m e n t , as s i x had l o s t t h e i r e l e c t r o d e a s s e m b l i e s and one i n t h e ABL-Cue group had f a i l e d t o d r i n k when s t i m u l a t i o n was r e d u c e d t o 2.5 uA. I n c l u d e d i n t h e a n a l y s i s a r e t h e d a t a from t h e 51 r a t s whose e l e c t r o d e t i p s ( c l o s e d symbols) were j u d g e d t o be i n o r on t h e b o r d e r s o f t h e two t a r g e t a r e a s . To f a c i l i t a t e p r e s e n t a t i o n o f t h e d a t a and t o a d j u s t f o r t h e s l i g h t d i f f e r e n c e s i n f l u i d i n t a k e b e f o r e c o n d i t i o n i n g , t h e r e t e n t i o n and e x t i n c t i o n i n t a k e s a r e e x p r e s s e d as p e r c e n t a g e s o f t h e p r e - L i C l i n t a k e , as measured i n the c o n d i t i o n i n g s e s s i o n . These i n t a k e s c o r e s a r e p r e s e n t e d g r a p h i c a l l y i n F i g . 8. A r e p e a t e d measures ANOVA o f t h e s e d a t a showed s i g n i f i c a n t main e f f e c t s f o r t r e a t m e n t s (F(6.51)=10.64, p < . 0 1 ) , t e s t s (F(3,153)=15.58, p < . 0 1 ) , and t h e i n t e r a c t i o n term (F(18,153)=3.19, p < . 0 1 ) . As i n E x p e r i m e n t I , a 1-way ANOVA f o r t r e a t m e n t e f f e c t s was a p p l i e d t o each t e s t day, and, when s i g n i f i c a n t m ain e f f e c t s were o b s e r v e d , Duncan's New M u l t i p l e Range t e s t was a p p l i e d t o d e t e r m i n e where t h e d i f f e r e n c e s between t r e a t m e n t groups o c c u r r e d , a t t h e 5% l e v e l o f s i g n i f i c a n c e . These 1-way ANOVA showed s i g n i f i c a n t t r e a t m e n t e f f e c t s on t h e r e t e n t i o n and f i r s t two e x t i n c t i o n t e s t s . As may be seen i n F i g . 8, t h e SAC-Cue and ABL-Cue groups consumed l e s s t h a n t h e o o t h e r groups i n t h e r e t e n t i o n t e s t - , a l t h o u g h t h e ABL-Cue group d r a n k more t h a n t h e SAC-Cue group. I n t h e f i r s t e x t i n c t i o n t e s t , t h e SAC-Cue and 46 F i g u r e 7. E l e c t r o d e p l a c e m e n t s o f t h e i m p l a n t e d r a t s i n E x p e r i m e n t I I I : CD-Cue and ABL-Cue, s t i m u l a t i o n o f c a u d a t e o r amygdala d u r i n g w a t e r d r i n k i n g on t h e 4 r e t e s t days (9, 11, 13, and 1 5 ) , a f t e r h a v i n g been f o l l o w e d by L i C l i n j e c t i o n on day 7 ( " c o n d i t i o n i n g " ) ; CD-Stim and A B L - S t i m , s t i m u l a t i o n d u r i n g w a t e r d r i n k i n g on t h e 4 r e t e s t d a y s , w i t h N a C l i n j e c t i o n on day 7; CD-Impl and A B L - I m p l , no s t i m u l a t i o n a t any t i m e , w i t h L i C l i n j e c t i o n on day 7. C l o s e d symbols i n d i c a t e p l a c e m e n t s j u d g e d t o be i n t h e t a r g e t a r e a s ; open symbols i n d i c a t e " m i s s e d " p l a c e m e n t s , w i t h t h e d a t a o f t h e s e r a t s o m i t t e d from t h e a n a l y s i s . B r a i n s e c t i o n s were t a k e n from P e l l e g r i n o and Cushman ( 1 9 6 7 ) . 47 48 F i g u r e 8. Mean f l u i d i n t a k e s on t e s t days 9, 11, 13, and 15, e x p r e s s e d p e r c e n t a g e s o f i n t a k e s on day 7, " c o n d i t i o n i n g " , p r i o r t o L i C l o r N a C l i n j e c t i o n s . F o r e x p l a n a t i o n s o f t h e t r e a t m e n t s , see F i g . 7 and t e x t . PERCENTAGE OF P R E - INJECTION INTAKE 6<7 50 ABL-Cue groups a g a i n d i f f e r e d f r o m t h e r e s t o f t h e g r o u p s , but n o t f r o m each o t h e r . The SAC-Cue group d i f f e r e d f r o m t h e ABL-Impl, CD-Impl, and CD-Cue groups i n t h e second e x t i n c t i o n t e s t . I n summary, t h e ABL-Cue group showed a s u p p r e s s i o n o f d r i n k i n g t h a t was v e r y s i m i l a r t o t h a t seen i n t h e SAC-Cue group: (1) v e r y low i n t a k e i n t h e r e t e n t i o n and f i r s t e x t i n c t i o n t e s t s , r e l a t i v e t o t h e u n p o i s o n e d (ABL-Stim and CD-Stim) o r u n s t i m u l a t e d (ABL-Impl and CD-Impl) g r o u p s , (2) i n c r e a s e d i n t a k e from t h e f i r s t t o t h e t h i r d e x t i n c -t i o n t e s t s , and (3) e v e n t u a l r e c o v e r y o f c o n s u m p t i o n t o 87.4% o f t h e p r e - L i C l l e v e l , as compared t o 91.6% f o r t h e SAC-Cue group. T a b l e 3 p r e s e n t s a summary of t h e w a t e r and s a c c h a r i n i n t a k e s on days .661-55 • I t s h o u l d be p o i n t e d out t h a t w a t e r d r i n k i n g was s u p p r e s s e d by a m y g d a l o i d s t i m u l a t i o n i n t h e u n p o i s o n e d c o n t r o l g r o u p , A B L - S t i m , t h r o u g h o u t t h e 5 t e s t days ( 7 , 9, 11, 13, and 1 5 ) . T h i s s u g g e s t s t h a t t h e i n i t i a l drop i n f l u i d i n t a k e i n t h i s group and i n t h e ABL-Cue group was due t o an i n t e r -f e r e n c e w i t h d r i n k i n g t h a t d i d n o t h a b i t u a t e o v e r t h e f o u r r e m a i n i n g t e s t d a y s , as would a neopho.bic r e s p o n s e t o a n o v e l t a s t e s t i m u l u s ( c f . , S A C - C n t l group i n F i g . 2 ) . By c o m p a r i s o n , t h e ABL-Impl group showed no suc h s y s t e m a t i c s u p p r e s s i o n o f d r i n k i n g , nor d i d t h e 3 c a u d a t e g r o u p s , a l t h o u g h t h e CD-Impl group showed a t r a n s i e n t s u p p r e s s i o n on t h e day a f t e r L i C l p o i s o n i n g . These o b s e r v a t i o n s , however, do n o t e x p l a i n t h e g r e a t e r s u p p r e s s i o n of d r i n k i n g seen i n the ABL-Cue group on t h e " r e t e n t i o n " day, and t h e g r a d u a l r e c o v e r y of w a t e r d r i n k i n g , i n t h e p r e s e n c e o f c o n c u r r e n t a m y g d a l o i d s t i m u l a t i o n , t o t h e p r e - L i C l l e v e l o f i n t a k e . Hence, t h e p r i m a r y c o n c l u s i o n of t h i s e x p e r i m e n t r e m a i n s unmoved: t h e i n t a k e o f " s t i m u l a t i o n - f l a v o r e d " w a t e r f o l l o w e d a p a t t e r n s i m i l a r to t h a t of " s a c c h a r i n - f l a v o r e d " w a t e r , when f o l l o w e d by L i C l p o i s o n i n g . TABLE 3. MEAN (+ STANDARD ERROR) FLUID INTAKE IN EXPERIMENT I I I T e s t Days S A C - C u e ^ ) 1 ABL-Cue(9) A B L - S t i m ( l O ) ABL-Impl (8 ) CD--Cue(9) CD-Stim(7) CD--Impl(8) Water 13.1C+1.0) 13.8(+0.6) 14.6C+0.7) 15.3C+0.7) 14.0C+0.8) 13.6(+0.7) 13 .4(+1.7) C o n d i t i o n i n g 9 , 5 ( + l . l ) 9.9 (±1Q0)_ 12.2(+1.2) 14.2(+0.7) 12 .8C+1.D 14.4(+0.9) 14 .3(+1.7) Water 15.5(+1.4) 12.8(+0.8) 15.1(+0.7) 12.8(+0.3) 11 .7(+1.2) 13.5(+0.8) 10 .3(+1.4) R e t e n t i o n 0.7(+0.1) 3.8(+0.8) 10.2(+1.6) 12.4(+0.8) 13 . 3 ( + l . l ) 14.8(+1.0) 13 .4(+1.5) Water 15.9(+0.9) 13.2(+0.4) 14.6(+0.5) 13.9(+0.4) 14 .K+1.0) 13.9(+0.7) 14 . 4 ( + l . l ) E x t i n c t i o n 1 1 .5(+0 .6) 4.9(+1.4) 10.2(+1.3) 14.4(+0.8) 14 .6(+1.0) 13.6(+0.9) 14 . 9 ( + l . l ) Water i7.o;(+i.o) 11.5(+1.5) 14.9(+0.9) 13.4(+0.9) 14 .4(+0.9) 13.7(+0.8) 14 .2(+1.4) E x t i n c t i o n 2 5.4(+1.8) 7.2(+1.7) 11.4(+1.8) 15.0(+0.7) 14 .6(+0.9) 13.9 £0.5) 14 .4(+1.1) Water 17.2(+1.0) 14.6(+0.6) 17.6(+0.9) 14.4(+0.8) 15 .9(+1.3) 13.9(+0.5) 15 .5(+0.9) E x t i n c t i o n 3 9.00+2.5) 8.7(+1.3) 10.9(+1.7) 15.0(+0.6) 15 .7(+0.8) 14.3(+0.6) 15 .3(+0.8) See F i g . 7 and t e x t f o r e x p l a n a t i o n s o f t h e t r e a t m e n t g r o u p s . 52 D i s c u s s i o n These r e s u l t s s t r o n g l y s u g g e s t t h a t a m y g d a l o i d s t i m u l a t i o n a c t e d as a c o n d i t i o n e d s t i m u l u s f o r l i t h i u m i l l n e s s i n t h i s and t h e p r e c e d i n g two e x p e r i -ments. The s u p p r e s s i o n o f d r i n k i n g " s t i m u l a t i o n - f l a v o r e d " w a t e r a f t e r a L i C l i n j e c t i o n , ( t h e ABL-Cue group) was s i m i l a r t o t h a t seen i n r a t s d r i n k i n g " s a c c h a r i n - f l a v o r e d " w a t e r as a cue f o r l i t h i u m i l l n e s s ( t h e SAC-Cue g r o u p ) . A d e t a i l e d e x a m i n a t i o n o f t h e d r i n k i n g o f t h e s u b j e c t s a c r o s s t h e 5 t e s t days c o n f i r m e d t h a t t h i s r e s p o n s e showed a c h a r a c t e r i s t i c i n i t i a l s u p p r e s s i o n d u r -i n g t h e r e t e n t i o n t e s t and a / g r a d u a l r e c o v e r y t o p r e - L i C l i n t a k e l e v e l s , com-p a r a b l e t o t h e p a t t e r n o f c o n d i t i o n e d a v e r s i o n and e x t i n c t i o n seen i n t h e SAC-Cue group. However, t h e s u p p r e s s i o n o f d r i n k i n g i n t h e p r e s e n c e of t h e ESB cue was n o t as g r e a t , as t h e ABL-Cue group d r a n k more t h a n t h e SAC-Cue group i n t h e r e t e n t i o n and f i r s t two e x t i n c t i o n t e s t s . T h i s s u g g e s t e d t h a t t h e ESB p r o v i d e d a weaker cue t h a n t h e t a s t e s t i m u l u s , a l t h o u g h t h e d i f f e r e n c e s i n t h e e x t i n c t i o n t e s t s d i d n o t r e a c h s t a t i s t i c a l s i g n i f i c a n c e . F u r t h e r m o r e , t h e s e d a t a , a l o n g w i t h t h o s e of E x p e r i m e n t I I , a r e i n c o m p a t i b l e w i t h e x p l a n a t i o n s w h i c h a t t r i b u t e t h e decrement i n t a s t e a v e r s i o n p e r f o r m a n c e t o a g e n e r a l d e f i c i t of memory f o r m a t i o n i n d u c e d by a m y g d a l o i d s t i m u l a t i o n . I n E x p e r i m e n t I , and p o s s i b l y i n r e l a t e d s t u d i e s ( A r t h u r , 1975; K e s n e r e t a l , , 1 975), memory f u n c t i o n s may w e l l have been i n t a c t when t h e amygdala was s t i m u l a t e d , b u t s i n c e an a v e r s i o n was c o n d i t i o n e d t o t h e s t i m u l u s compound ( t a s t e p l u s ESB), r e t e n t i o n appeared t o be poor when one element (ESB) was a b s e n t i n t h e r e t e s t . The r e s u l t s o f t h e r e m a i n i n g 5 t r e a t m e n t g r o u p s s u g g e s t t h a t t h e e f f e c t o b s e r v e d i n t h e ABL-Cue group c o u l d n o t be a t t r i b u t e d t o n o n s p e c i f i c e f f e c t s of s t i m u l a t i o n o r i m p l a n t a t i o n . The A B L - S t i m and CD-Stim d a t a showed t h a t w i t h o u t t h e L i C l i n j e c t i o n t h e r e p e a t e d i n t r a c r a n i a l s t i m u l a t i o n , a p p l i e d d u r i n g c o n d i t i o n i n g and e a c h r e t e s t , d i d n o t p r o d u c e a s y s t e m a t i c d e c r e a s e i n 53 f l u i d i n t a k e t h a t may haye been due t o s e n s i t i z a t i o n t o t h e ESB o r t o com-p e t i n g r e s p o n s e s , s u c h as r e a r i n g and e x p l o r i n g , e l i c i t e d by s t i m u l a t i o n . The ABL-Impl and CD-Impl d a t a showed t h a t t h e trauma o f t h e s u r g i c a l p r o c e d u r e and i m p l a n t a t i o n d i d n o t r e s u l t i n a d e c r e a s e d f l u i d i n t a k e t h a t would a c c o u n t f o r t h e s y s t e m a t i c s u p p r e s s i o n seen i n t h e ABL-Cue group, a f t e r t h e L i C l i n j e c t i o n . F i n a l l y , t h e CD-Cue d a t a showed t h a t t h e e f f e c t seen i n t h e ABL-Cue group was c l e a r l y l o c u s - s p e c i f i c , d e s p i t e t h e f a c t t h a t CD s t i m u l a t i o n had s e r v e d as a v e r y e f f e c t i v e means of d i s r u p t i n g shock a v o i d a n c e b e h a v i o r i n E x p e r i m e n t I . 54 GENERAL DISCUSSION The r e s u l t s of E x p e r i m e n t I c o n f i r m e d , f o r t h e most p a r t , t h e p r e d i c t i o n s based on e a r l i e r s t u d i e s . L o w - i n t e n s i t y e l e c t r i c a l s t i m u l a t i o n o f t h e CD and SNC d u r i n g t r a i n i n g i n t h e stepdown shock a v o i d a n c e t a s k d i s r u p t e d r e t e n t i o n when t e s t e d 24 h r l a t e r , w h i l e t h e same s t i m u l a t i o n a p p l i e d d u r i n g t a s t e a v e r s i o n c o n d i t i o n i n g had no e f f e c t on t h e subsequent a v e r s i o n t o s a c c h a r i n . These d a t a c o n f i r m e d t h e p r e d i c t i o n t h a t e x t r a p y r a m i d a l s t i m u l a t i o n would have l i t t l e o r no e f f e c t on CTA. Hence, t h e e f f e c t s of s t i m u l a t i o n i n t h e s e two e x t r a p y r a m i d a l motor a r e a s seem t o be s p e c i f i c t o s hock a v o i d a n c e t a s k s , and do n o t g e n e r a l i z e t o t a s t e a v e r s i o n l e a r n i n g . The r e s u l t s o b t a i n e d w i t h amygda-l o i d s t i m u l a t i o n extended t h e f i n d i n g s o f e a r l i e r s t u d i e s . B r e s n e h a n and R o u t t e n b e r g (1972) r e p o r t e d t h a t w h i l e s t i m u l a t i o n o f t h e m e d i a l amygdala p r o -duced a d e f i c i t i n stepdown r e t e n t i o n , . ABL s t i m u l a t i o n appeared t o be much l e s s e f f e c t i v e . However, s i n c e t h e r e were o n l y a few p l a c e m e n t s i n t h e ABL a r e a , t h e l a t t e r s u g g e s t i o n was t e n t a t i v e . The p r e s e n t r e s u l t s c l e a r l y showed t h a t ABL s t i m u l a t i o n p r o duced a s i g n i f i c a n t i m p a i r m e n t i n r e t e n t i o n o f a stepdown p a s s i v e a v o i d a n c e r e s p o n s e . Whether s u c h d e f i c i t s a r e due t o s t i m u l u s c o n t r o l , as s u g g e s t e d f o r s i m i l a r f i n d i n g s i n t a s t e a v e r s i o n , w i l l have t o a w a i t t h e r e s u l t s of f u r t h e r e x p e r i m e n t s . W i t h r e g a r d t o t a s t e a v e r s i o n l e a r n i n g , e a r l i e r s t u d i e s have shown t h a t a m y g d a l o i d s t i m u l a t i o n i s e f f e c t i v e when a p p l i e d a f t e r t h e L i C l a d m i n i s t r a t i o n (Kesner et a l . , 1975) o r i n t h e i n t e r v a l between t h e t a s t e CS and t h e i l l n e s s US ( A r t h u r , 1 9 75), a l t h o u g h i n t h e l a t t e r c a s e t h e s t i m u l a t i o n c u r r e n t was h i g h enough (115 uA) t o e l i c i t s e i z u r e a c t i v i t y . These s t u d i e s have s u g g e s t e d t h a t n o r m a l f u n c t i o n i n g of t h e amygdala a f t e r t h e t a s t e e x p e r i e n c e i s n e c e s s a r y f o r t h e development of t a s t e a v e r s i o n , but t h e e f f e c t o f a p p l y i n g s t i m u l a t i o n d u r i n g c o n s u m p t i o n of t h e s a c c h a r i n s o l u t i o n was l e f t u n r e s o l v e d . The p r e s e n t 55 p r o c e d u r e employed v e r y l ow c u r r e n t i n t e n s i t i e s (2-10 u A ) , t h e r e b y p e r m i t t i n g t h e a n i m a l s t o d r i n k a t t h e same ti m e t h a t s t i m u l a t i o n was b e i n g a p p l i e d . I n t h i s way, t h e e f f e c t s o f a m y g d a l o i d s t i m u l a t i o n a p p l i e d d u r i n g t h e CS p e r i o d c o u l d be e v a l u a t e d w i t h r e s p e c t t o o t h e r f u n c t i o n s . F u r t h e r m o r e , t h e e x t e n s i o n of t h i s p r o c e d u r e i n E x p e r i m e n t I I showed t h a t s i m i l a r l o w - i n t e n s i t y s t i m u l a -t i o n was d i s r u p t i v e when a p p l i e d d u r i n g t h e i n t e r s t i m u l u s i n t e r v a l , o r d u r i n g t h e o n s e t o f t h e l i t h i u m - i n d u c e d i l l n e s s . A m y g d a l o i d s t i m u l a t i o n a d m i n i s t e r e d d u r i n g t h e r e t e n t i o n t e s t had no e f f e c t on CTA. A f u r t h e r e x t e n s i o n o f t h i s a n a l y s i s r e v e a l e d perhaps t h e most i m p o r t a n t o b s e r v a t i o n i n t h i s s t u d y : a n i m a l s r e c e i v i n g s t i m u l a t i o n d u r i n g b o t h a c q u i s i t i o n and r e t e n t i o n showed n o r m a l t a s t e a v e r s i o n s . I n l i g h t o f t h i s f i n d i n g , i t i s d o u b t f u l t h a t t h e d i s -r u p t i o n o f memory p r o c e s s e s can a c c o u n t f o r a l l t h e d e f i c i t s i n t a s t e a v e r s i o n p r o d uced by ESB d u r i n g t h e d i f f e r e n t phases of a c q u i s i t i o n . The e f f e c t s o f l o c a l i z e d l o w - i n t e n s i t y ESB on b e h a v i o r d i s p l a y e d i n sub-sequent r e t e s t s have been i n t e r p r e t e d t r a d i t i o n a l l y i n l i g h t o f memory s t o r a g e and r e t r i e v a l p r o c e s s e s . F o r example, K e s n e r (1977) has argued t h a t s u c h • s t i m u l a t i o n can be used t o d e f i n e t h e i n v o l v e m e n t o f n e u r a l s t r u c t u r e s i n v a r i o u s a s p e c t s o f short-aaridl'long-=terminmemory. An i n t r i g u i n g a l t e r n a t i v e e x p l a n a t i o n i s s u g g e s t e d by t h e o b s e r v a t i o n s t h a t a n i m a l s s t i m u l a t e d d u r i n g a c q u i s i t i o n and r e t e n t i o n d i s p l a y e d t a s t e a v e r s i o n s and t h a t s t i m u l a t i o n o f t h e ABL was shown t o s e r v e as a CS i n a CTA paradigm. T h i s e x p l a n a t i o n i s based on t h e a s s u m p t i o n t h a t ESB i n a r e g i o n t o w h i c h t a s t e i n f o r m a t i o n i s t r a n s m i t t e d ( N o r g r e n , 1976) can s e r v e as a cue o r CS, w h i c h can be a s s o c i a t e d w i t h i l l n e s s . T h i s s u g g e s t i o n i s e n t i r e l y c o n s i s t e n t w i t h t h e w e l l - e s t a b l i s h e d f i n d i n g t h a t ESB can be used as c o n d i t i o n e d and d i s c r i m i n a t i v e s t i m u l i i n c l a s s i c a l and o p e r a n t c o n d i t i o n i n g s i t u a t i o n s . ( C o l a v i t a and S z e l i g o , 1971; E l s t e r , V a n D e r c a r , and Schneiderman, 1970; f o r a r e v i e w o f t h e p r e v i o u s l i t e r a t u r e , see Doty, 1969). The p r e s e n t a t i o n o f s u c h ESB d u r i n g a c q u i s i t i o n 56 of t a s t e a v e r s i o n c o u l d t h e r e f o r e f o r m a s t i m u l u s compound ( B a k e r , 1 9 6 8 ) , i n c o n j u n c t i o n w i t h t h e t a s t e s t i m u l u s , t o w h i c h t h e a v e r s i o n would s u b s e q u e n t l y be c o n d i t i o n e d . T h i s c o n c l u s i o n a l l o w s one t o i n t e r p r e t t h e p r e s e n t d a t a i n terms of s t i m u l u s c o n t r o l r a t h e r t h a n i m p a i r m e n t o f memory f o r m a t i o n . There have been many a t t e m p t s t o e x p l a i n how a n i m a l s r e s p o n d t o a s t i m u l u s complex, w i t h t h e most common a s s u m p t i o n b e i n g t h a t t h e r e s p o n s e t o t h e com-pound r e f l e c t s l e a r n i n g about t h e i n d i v i d u a l e l e m e n t s ( E s t e s , 1950; H u l l , 1 9 4 3 ) . However, R e s c o r l a (1972) has p r e s e n t e d s e v e r a l examples o f r e s p o n d i n g t o a s t i m u l u s complex t h a t cannot be i n t e r p r e t e d as a c o m b i n a t i o n o f t h e a s s o c i a - . t i v e s t r e n g t h s o f t h e r e s p o n s e s t o t h e i n d i v i d u a l s t i m u l i . F o r example, a n i m a l s were t r a i n e d s u c c e s s f u l l y t o d i s c r i m i n a t e between a compound and i t s e l e m e n t s , r e g a r d l e s s of whether t h e compound o r t h e e l e m e n t s were r e i n f o r c e d . R e s c o r l a , (1972) has s u g g e s t e d t h a t " s t i m u l u s compounds" s h o u l d be t r e a t e d as t h e c o m b i n a t i o n o f t h e i r e l ements p l u s some s t i m u l u s w h i c h i s q u n i q u e l y g e n e r a t e d whenever t h o s e e l e m e n t s a r e p r e s e n t e d t o g e t h e r . A l t h o u g h R e s c o r l a (1972) a r g u e s t h a t t h e compound r e p r e s e n t s more t h a n t h e sum o f i t s e l e m e n t s , he emphasizes t h a t t h i s does n o t i n v o l v e d e s t r u c t i o n of t h e i n t e g r i t y o f t h e i n d i v i d u a l e l e m e n t s . The p r e s e n t r e s u l t s appear t o c o n f i r m b o t h a s s e r t i o n s . S t i m u l a t i o n of t h e amygdala p l u s t h e t a s t e o f s a c -c h a r i n a r e v i e w e d as a s t i m u l u s compound w i t h a u n i q u e a s s o c i a t i o n w i t h i l l -n e s s . I t i s n o t s u r p r i s i n g , t h e r e f o r e , t h a t an a n i m a l would show a g r e a t l y a t t e n u a t e d a v e r s i o n when t h e compound i s d i v i d e d and o n l y t h e t a s t e cue i s p r e s e n t e d d u r i n g r e t e s t i n g . I t s h o u l d be r e c a l l e d t h a t t h e ESB-cue e f f e c t a p p e a r s t o be s p e c i f i c a l l y a s s o c i a t e d w i t h t h e amygdala, o r a t l e a s t t h o s e p o r t i o n s o f t h e b r a i n i n v o l v e d i n p r o c e s s i n g g u s t a t o r y i n f o r m a t i o n . As s u c h , s t i m u l a t i o n o f t h e amygdala may f o r m a u n i q u e compound w i t h t a s t e , a compound w i t h d i f f e r e n t p r o p e r t i e s t h a n t h o s e r e s u l t i n g f r o m a c o m b i n a t i o n of c 57 "natural" s t i m u l i . The assertion that the i n t e g r i t y of the i n d i v i d u a l elements i s maintained i n the compound, or "configure", also i s supported by the r e s u l t of the SACC treatment i n Experiment I. When saccharin i s the only element present i n the r e t e s t , a weak, but nevertheless s i g n i f i c a n t , aversion i s seen, as compared to the p o s i t i v e preference s h i f t shown by the unpoisoned saccharin controls (see F i g . 2). The apparent demonstration of co n f i g u r a l conditioning i n the present series of experiments i s unique i n that t h i s type of conditioning has not been demonstrated with ESB as the CS. More importantly, c o n f i g u r a l condi-tioning has not been demonstrated within a s i n g l e t r i a l with no. p r i o r r e i n -forcement of the elements of a compound. As such, these findings represent another important extension of our knowledge of animal learning, derived from the use of the conditioned taste aversion paradigm. 58 REFERENCES A r t h u r , J.B. T a s t e a v e r s i o n l e a r n i n g i s i m p a i r e d by i n t e r p o l a t e d a m y g d a l o i d s t i m u l a t i o n b u t n o t by p o s t t r a i n i n g a m y g d a l o i d s t i m u l a t i o n . B e h a v i o u r a l  B i o l o g y , 1975, 13, 369-376. B a k e r , T.W. P r o p e r t i e s o f compound c o n d i t i o n e d s t i m u l i and t h e i r components. P s y c h o l o g i c a l B u l l e t i n , 1968, 70, 611-625. B a l a g u r a , S., R a l p h , T.L., and G o l d , R. E f f e c t o f e l e c t r i c a l b r a i n s t i m u l a t i o n of d i e n c e p h a l i c and m e s e n c e p h a l i c s t r u c t u r e s on t h e g e n e r a l i z e d N a C l a v e r s i o n a f t e r L i C l p o i s o n i n g . P h y s i o l o g i s t , 1972, 15, 77. B e a t t y , W.W., and Schwartzbaum, J.S. Enhanced r e a c t i v i t y t o q u i n i n e and s a c c h a r i n s o l u t i o n s f o l l o w i n g s e p t a l l e s i o n s i n t h e r a t . Psychonomic S c i e n c e , 1968, 8, 483-484. B e s t , P . J . , and O r r , J . E f f e c t s o f h i p p o c a m p a l l e s i o n s on p a s s i v e a v o i d a n c e and t a s t e a v e r s i o n c o n d i t i o n i n g . P h y s i o l o g y and B e h a v i o r , 1973, LO, 193-196. Braneman, N., and C a p r e t t a , P . J . The r e l a t i v e e f f e c t i v e n e s s o f two e x p e r i -m e n t a l t e c h n i q u e s f o r t h e m o d i f i c a t i o n o f f o o d p r e f e r e n c e s i n r a t s . P r o c e e d i n g s o f t h e 73rd A n n u a l C o n v e n t i o n o f t h e A m e r i c a n P s y c h o l o g i c a l  A s s o c i a t i o n , 1965, pp. 129-130. Bresnehan, E., and R o u t t e n b e r g , A. Memory d i s r u p t i o n by u n i l a t e r a l l o w - l e v e l , s u b s e i z u r e s t i m u l a t i o n o f t h e m e d i a l a m y g d a l o i d n u c l e u s . P h y s i o l o g y and B e h a v i o r , 1972, _9, 513-525. B r u n n e r , R.L., R o s s i , R.R., S t u t z , R.M., and R o t h , T.G. Memory l o s s f o l l o w i n g p o s t t r i a l e l e c t r i c a l s t i m u l a t i o n o f t h e hippocampus. Psychonomic S c i e n c e , 1970, 18, 159-160. C o l a v i t a , F.B., and S z e l i g o , F. C l a s s i c a l c o n d i t i o n i n g w i t h b r a i n s t i m u l a t i o n a t one s i t e s e r v i n g as b o t h CS and US. P h y s i o l o g y and B e h a v i o r , 1971, 6_, 41-44. C o s c i n a , D.V., and B a l a g u r a , S. A v o i d a n c e and escape b e h a v i o r i n r a t s w i t h a p h a g i a produced by b a s a l d i e n c e p h a l i c l e s i o n s . P h y s i o l o g y and B e h a v i o r , 1970, 5, 651-657. Cowan, W.M., Raisman, G., and P o w e l l , T.P.S. The c o n n e x i o n s o f t h e amygdala. J o u r n a l o f N e u r o l o g y , N e u r o s u r g e r y and P s y c h i a t r y , 1965, 28^, 137-151. D e v e n p o r t , L.D., and B a l a g u r a , S. L a t e r a l h y pothalamus: R e e v a l u a t i o n o f f u n c t i o n i n m o t i v a t e d f e e d i n g b e h a v i o r . S c i e n c e , 1971, 17.2, 744-746. D i e t z , M.N., and C a p r e t t a , P . J . M o d i f i c a t i o n o f sugar and s u g a r - s a c c h a r i n p r e f e r e n c e i n r a t s as a f u n c t i o n o f e l e c t r i c a l s hock t o t h e mouth. P r o c e e d i n g s  of t h e 7 5 t h A n n u a l C o n v e n t i o n o f t h e A m e r i c a n P s y c h o l o g i c a l A s s o c i a t i o n , 1967, pp. 161-162. 59 Doty, R.W. E l e c t r i c a l s t i m u l a t i o n o f t h e b r a i n i n b e h a v i o r a l c o n t e x t . A n n u a l Review of P s y c h o l o g y , 1969, ^ 0 , 289-320. E l s t e r , A . J . , V a n D e r c a r , D.H., and Schneiderman, N, C l a s s i c a l c o n d i t i o n i n g of h e a r t r a t e d i s c r i m i n a t i o n s u s i n g s u b c o r t i c a l e l e c t r i c a l s t i m u l a t i o n as c o n d i t i o n e d and u n c o n d i t i o n e d s t i m u l i . P h y s i o l o g y , and B e h a v i o r , 1970, 5^ 503-508. E s t e s , W.K. Toward a s t a t i s t i c a l t h e o r y o f l e a r n i n g . P s y c h o l o g i c a l Review, 1950, 57, 94-107. F i b i g e r , H.C., and P h i l l i p s , A.G. R e t r o g r a d e amnesia a f t e r e l e c t r i c a l s t i m u -l a t i o n o f t h e s u b s t a n t i a n i g r a : M e d i a t i o n by t h e d o p a m i n e r g i c n i g r o - n e o s t r l a t a l b u n d l e . B r a i n R e s e a r c h , 1976, 116, 23-33. G a r c i a , J , , and K o e l l i n g , R.A.. The r e l a t i o n o f cue t o consequence i n a v o i d a n c e l e a r n i n g , Psychonomic S c i e n c e , 1966, 4_, 123-124. G a r c i a , J . , H a n k i n s , W.G., and R u s i n i a k , K.W. B e h a v i o r a l r e g u l a t i o n o f t h e m i l i e u i n t e r n e i n man and r a t . S c i e n c e , 1974, 185, 824-831. G a r c i a , J . , K i m e l d o r f , D.J., and K o e l l i n g , R.A. C o n d i t i o n e d a v e r s i o n t o s a c c h a r i n r e s u l t i n g f r o m e x p o s u r e t o gamma r a d i a t i o n . S c i e n c e , 1955, 122, 157-158. Goddard, G.V. A m y g d a l o i d s t i m u l a t i o n and l e a r n i n g i n t h e r a t . J o u r n a l o f  C o m p a r a t i v e and P h y s i o l o g i c a l P s y c h o l o g y , 1964, _58, 23-30. Goddard, G.V. Long term a l t e r a t i o n f o l l o w i n g a m y g d a l o i d s t i m u l a t i o n . I n B.E. E l e f t h e r i o u ( E d . ) , The N e u r o b i o l o g y o f t h e Amygdala.. New Y o r k : Plenum, 1972, Pp. 581-596. G o l d , P.E., and McGaugh, J . L . A s i n g l e - t r a c e , t w o - p r o c e s s v i e w o f memory s t o r a g e p r o c e s s e s . I n D. D e u t s c h and J.A. D e u t s c h ( E d s . ) , S h o r t - t e r m Memory, New Y o r k : Academic P r e s s , 1975, Pp. 355-378. G o l d , P.E., H a n k i n s , L.L., and Rose, R.P. Time-dependent p o s t - t r i a l changes i n t h e l o c a l i z a t i o n o f a m n e s t i c e l e c t r i c a l s t i m u l a t i o n s i t e s w i t h i n t h e amygdala i n r a t s . B e h a v i o r a l B i o l o g y , 1977, 20, 32-40. G o l d , P.E., M a c r i , J . , and McGaugh, J . L . R e t r o g r a d e amnesia produced by s u b s e i z u r e amygdala s t i m u l a t i o n . B e h a v i o r a l B i o l o g y , 1973, _9, 671-680, H a m i l t o n , L.W., and C a p o b i a n c o , S. Consumption o f sodium c h l o r i d e and l i t h i u m c h l o r i d e i n n o r m a l r a t s and i n r a t s w i t h s e p t a l l e s i o n s . P h y s i o l o g i c a l  P s y c h o l o g y , 1973, 1, 213-218. H e r z , M.J., M a r s h a l l , K.E., and Peeke, H.V.S. B r a i n s t i m u l a t i o n and b e h a v i o r : C o n t r o l s and consequences. P h y s i o l o g i c a l P s y c h o l o g y , 1974, _2, 184-186. Hobbs, J.H., E l k i n s , R.L., and P e a c o c k , L . J . T a s t e - a v e r s i o n c o n d i t i o n i n g i n r a t s w i t h s e p t a l l e s i o n s . B e h a v i o r a l B i o l o g y , 1974, _11, 239-245. H u l l , C.L. P r i n c i p l e s o f B e h a v i o r . New Y o r k : A p p l e t o n - C e n t u r y - C r o f t s , 1 9 4 3 v Pp. 47(,178. 60 Kaada, B.R. S t i m u l a t i o n and r e g i o n a l a b l a t i o n o f t h e a m y g d a l o i d complex w i t h r e f e r e n c e t o f u n c t i o n a l r e p r e s e n t a t i o n s . I n B.E. E l e f t h e r i o u ( E d . ) , The N e u r o b i o l o g y o f The Amygdala. New Y o r k : Plenum P r e s s , 1972, Pp. 205-281. Kapp, B.S., Kaufman, J.D., and R e p o l e , D.A. Hippocampal s t i m u l a t i o n and memory: E f f e c t s o f s t i m u l a t i o n p a r a m e t e r s and r e i n f o r c e m e n t m a g n i t u d e . P h y s i o l o g y  and B e h a v i o r , 1974, 13, 47-55. Kemble, E.D., and N a g e l , J.A. F a i l u r e t o f o r m a l e a r n e d t a s t e a v e r s i o n i n r a t s w i t h a m y g d a l o i d l e s i o n s . B u l l e t i n o f t h e Psychonomic S o c i e t y , 1973, 2^, 155-156. K e s n e r , R.P. A n e u r a l system a p p r o a c h t o t h e s t u d y o f memory s t o r a g e and r e t r i e v a l . I n R.R. D r u c k e r - C o l i n and J . L . McGaugh ( E d s . ) , The N e u r o b i o l o g y  SffeSleep and Memory. New Y o r k : Academic P r e s s , 1977. Pp. 227-254. K e s n e r , R.P., and Berman, R.F. E f f e c t s o f m i d b r a i n r e t i c u l a r f o r m a t i o n , h i p p o c a m p a l , and l a t e r a l h y p o t h a l a m i c s t i m u l a t i o n upon r e c o v e r y f r o m neo-p h o b i a and t a s t e a v e r s i o n l e a r n i n g . P h y s i o l o g y and B e h a v i o r , 1977, 18_, 763-768. K e s n e r , R.P., and Conner, H.S. Independence o f s h o r t - and l o n g - t e r m memory: A n e u r a l systems a n a l y s i s . S c i e n c e , 1972, 176, 432-434. K e s n e r , R.P., and D o t y , R.W. Amnesia p r o d u c e d i n c a t s by l o c a l s e i z u r e a c t i v i t y i n i t i a t e d f rom t h e amygdala. E x p e r i m e n t a l N e u r o l o g y , 1968, 21, 58-68. K e s n e r , R.P., and W i l b u r n , M.W. A r e v i e w of e l e c t r i c a l s t i m u l a t i o n o f t h e b r a i n i n c o n t e x t o f l e a r n i n g and r e t e n t i o n . B e h a v i o r a l B i o l o g y , 1974, 10, 259-293. K e s n e r , R.P., Berman, R.F., B u r t o n , B., and H a n k i n s , W.G. E f f e c t s o f e l e c t r i c a l s t i m u l a t i o n of amygdala upon n e o p h o b i a and t a s t e a v e r s i o n . B e h a v i o r a l B i o l o g y , 1975, 13, 349-358. K r a n e , R.V., and Wagner, A.R. T a s t e a v e r s i o n l e a r n i n g w i t h a d e l a y e d shock US: I m p l i c a t i o n s f o r t h e " g e n e r a l i t y o f t h e l a w s of l e a r n i n g " . J o u r n a l o f  C o m p a r a t i v e and P h y s i o l o g i c a l P s y c h o l o g y , 1975, 8*3, 882-889. L a r s e n , J.D., and Hyde, T.S. A c o m p a r i s o n o f l e a r n e d a v e r s i o n s t o g u s t a t o r y and e x t e r o c e p t i v e cues i n r a t s . A n i m a l L e a r n i n g and B e h a v i o r , 1977, _5, 17-20. L e t t , B.T., and H a r l e y , C.W. S t i m u l a t i o n o f l a t e r a l hypothalamus d u r i n g s i c k n e s s a t t e n u a t e s l e a r n e d f l a v o r a v e r s i o n . P h y s i o l o g y and B e h a v i o r , 1974, 12, 79-83. L i d s k y , T . I . , L e v i n e , M.S., K r e i n i c k , C . J . , and Schwartzbaum, J.S. R e t r o g r a d e e f f e c t s of a m y g d a l o i d s t i m u l a t i o n on c o n d i t i o n e d s u p p r e s s i o n (CER) i n r a t s . J o u r n a l o f C o m p a r a t i v e and P h y s i o l o g i c a l P s y c h o l o g y , 1970, 7_3» 135-149. Luna, L.G. ( E d . ) , Manual of H i s t o l o g i c a l S t a i n i n g Methods of The Armed F o r c e s  I n s t i t u t e o f P a t h o l o g y . New Y o r k : M c G r a w - H i l l , 1968. 61 M a c k i n t o s h , N.J. A t h e o r y o f a t t e n t i o n : V a r i a t i o n s i n . t h e a s s o c i a b i l i t y o f s t i m u l i w i t h r e i n f o r c e m e n t . P s y c h o l o g i c a l Review, 1975, 82_, 276-298. Mahut, H. E f f e c t s o f s u b c o r t i c a l e l e c t r i c a l s t i m u l a t i o n on l e a r n i n g i n t h e r a t . J o u r n a l o f C o m p a r a t i v e and P h y s i o l o g i c a l P s y c h o l o g y , 1962, \5_5_, 472-477. M c C l e a r y , R.A. Response m o d u l a t i n g f u n c t i o n s o f t h e l i m b i c system: i n i t i a t i o n and s u p p r e s s i o n . I n E. S t e l l a r and J.M. Sprague ( E d s . ) , P r o g r e s s i n P h y s i o l  l o g i c a l P s y c h o l o g y , V o l . 1. New Y o r k : Academic P r e s s , 1966. Pp. 209-272. McGaugh, J . L . , and G o l d , P.E. M o d u l a t i o n o f memory p r o c e s s e s w i t h e l e c t r i c a l s t i m u l a t i o n o f t h e b r a i n . I n M.R. Rosenzweig and E.L. Bennet ( E d s . ) , N e u r a l  Mechanisms o f L e a r n i n g and Memory. Cambridge: The MIT P r e s s , 1976. Pp.549-560. McGowan, B.K., H a n k i n s , W.G., and G a r c i a , J . L i m b i c l e s i o n s and c o n t r o l o f the i n t e r n a l and e x t e r n a l e n v i r o n m e n t . B e h a v i o r a l B i o l o g y , 1972, 7_, 841-852. McGowan, B.K., G a r c i a , J . , E r v i n , F.R., and S c h w a r t z , J . E f f e c t s o f s e p t a l l e s i o n s on b a i t - s h y n e s s i n t h e r a t . P h y s i o l o g y and B e h a v i o r , 1969, 4_, 907-909. M i k u l k a , P . J . , Freeman, F.G., and L i d s t r o m , P. The e f f e c t o f t r a i n i n g t e c h n i q u e and amygdala l e s i o n s on t h e a c q u i s i t i o n and r e t e n t i o n o f a t a s t e a v e r s i o n . B e h a v i o r a l B i o l o g y , 1977, _19_, 509-517. M i l l e r , C.R., E l k i n s , R.L., and Peac o c k , L . J . D i s r u p t i o n o f r a d i a t i o n -i n d u c e d p r e f e r e n c e s h i f t by h i p p o c a m p a l l e s i o n s . P h y s i o l o g y and B e h a v i o r , 1971, 6, 283-285. M M i l l e r , C?.R., E l k i n s , R.L. , F r a s e r , J . , Pea c o c k , L . J . , and Hobbs, S.H. T a s t e a v e r s i o n and p a s s i v e a v o i d a n c e i n r a t s w i t h h i p p o c a m p a l l e s i o n s . P h y s i o l o g i c a l P s y c h o l o g y , 197'5, 3., 123-126. M o r r i s o n , G.R., and C o l l y e r , R. T a s t e - m e d i a t e d c o n d i t i o n e d a v e r s i o n t o an e x t e r o c e p t i v e s t i m u l u s f o l l o w i n g L i C l p o i s o n i n g . J o u r n a l o f C o m p a r a t i v e and  P h y s i o l o g i c a l P s y c h o l o g y , 1974, 86^, 51-55. Murphy, L.R., and Brown, T.S. Hippocampal l e s i o n s and l e a r n e d t a s t e a v e r s i o n . P h y s i o l o g i c a l P s y c h o l o g y , 1974, 2_, 60-64. Nachman, M. L e a r n e d t a s t e and t e m p e r a t u r e a v e r s i o n s due t o L i C l s i c k n e s s a f t e r t e m p o r a l d e l a y s . J o u r n a l o f Comparative, and P h y s i o l o g i c a l P s y c h o l o g y , 1970, 7J3, 22-30. Nachman, M., and Ashe, J.H. L e a r n e d t a s t e a v e r s i o n s i n r a t s as a f u n c t i o n o f dosage, c o n c e n t r a t i o n , and r o u t e o f a d m i n i s t r a t i o n o f L i C l . P h y s i o l o g y . and B e h a v i o r , 1973, 10, 73-78. Nachman, M., and Ashe, J.H. E f f e c t s o f b a s o l a t e r a l amygdala l e s i o n s on n e o p h o b i a , l e a r n e d t a s t e a v e r s i o n s , and sodium a p p e t i t e i n r a t s . J o u r n a l o f  Co m p a r a t i v e and P h y s i o l o g i c a l P s y c h o l o g y , 1974, 87_, 622-643. N o r g r e n , R. T a s t e pathways t o t h e hypothalamus and amygdala. J o u r n a l o f  C o m p a r a t i v e N e u r o l o g y , 1976, 166, 17-30. 62 O v e r t o n , D.A. E x p e r i m e n t a l methods f o r t h e s t u d y o f s t a t e - d e p e n d e n t l e a r n i n g . F e d e r a t i o n P r o c e e d i n g s , 1974, 33, 1800-1813. P e l l e g r i n o , L. Amygdala l e s i o n s and b e h a v i o r a l i n h i b i t i o n i n t h e r a t . J o u r n a l o f C o m p a r a t i v e and P h y s i o l o g i c a l P s y c h o l o g y , 1968, J55, 483-491. P e l l e g r i n o , L., and Cushman, A. A S t e r e o t a x i c A t l a s o f The Rat B r a i n . New Y o r k : A p p l e t o n - C e n t u r y - C r o f t s , 1967. P h i l l i p s , A.G., and C l o u s t o n , R. D i s r u p t i o n of O n e - T r i a l A p p e t i t i v e L e a r n i n g  and P a s s i v e A v o i d a n c e F o l l o w i n g S t i m u l a t i o n o f t h e S u b s t a n t i a N i g r a P a r s  Compacta. S u b m i t t e d f o r p u b l i c a t i o n , 1977. R e s c o r l a , R.A. " C o n f i g u r a l " c o n d i t i o n i n g i n d i s c r e t e - t r i a l b a r p r e s s i n g . J o u r n a l o f C o m p a r a t i v e and P h y s i o l o g i c a l P s y c h o l o g y , 1972, 7_9, 307-317. Revusky, S.H. A v e r s i o n t o s u c r o s e produced by c o n t i n g e n t x - i r r a d i a t i o n : Temporal and dosage p a r a m e t e r s . J o u r n a l of C o m p a r a t i v e and P h y s i o l o g i c a l  P s y c h o l o g y , 1968, 65, 17-22. Revusky, S.H., and G a r c i a , J . L e a r n e d a s s o c i a t i o n s o v e r l o n g d e l a y s . I n G.H. Bower (Ed.), The P s y c h o l o g y of L e a r n i n g and M o t i v a t i o n : Advances i n  R e s e a r c h and Theory, V o l . 4 . New Y o r k : Academic P r e s s , 1970. Pp. 1-84. R o l l s , B . J . , and R o l l s , E.T^ E f f e c t s o f l e s i o n s i n t h e b a s o l a t e r a l amygdala on f l u i d i n t a k e i n t h e r a t . J o u r n a l o f C o m p a r a t i v e and P h y s i o l o g i c a l P s y c h o l o g y , 1973, 83, 240-247(a) R o l l s , E.T., and R o l l s , B . J . A l t e r e d f o o d p r e f e r e n c e s a f t e r l e s i o n s i n t h e b a s o l a t e r a l r e g i o n of t h e amygdala i n t h e r a t . J o u r n a l o f C o m p a r a t i v e and  P h y s i o l o g i c a l P s y c h o l o g y , 1973, 83, 2 4 8 - 2 5 9 ( b ) . R o t h , S.R., S c h w a r t z , M., and T e i t e l b a u m , P. F a i l u r e of r e c o v e r e d l a t e r a l h y p o t h a l a m i c r a t s t o l e a r n s p e c i f i c f o o d a v e r s i o n s . J o u r n a l o f C o m p a r a t i v e  and P h y s i o l o g i c a l P s y c h o l o g y , 1973, 83, 184-197. R o u t t e n b e r g , A., and Holzman, N. Memory d i s r u p t i o n 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 u b s t a n t i a n i g r a , p a r s compacta. S c i e n c e , 1973, 181, 83-86. R u n n e l s , R., and Thompson, R. H y p o t h a l a m i c s t r u c t u r e s c r i t i c a l f o r t h e p e r f o r m a n c e of a l o c o m o t o r escape r e s p o n s e i n t h e r a t . B r a i n R e s e a r c h , 1969, 13, 328-337. R z o s k a , J . B a i t s h y n e s s , a s t u d y i n r a t b e h a v i o r . The B r i t i s h J o u r n a l o f  A n i m a l B e h a v i o r , 1953, 1^ , 128-135. S a n t o s - A n d e r s o n , R.M., and R o u t t e n b e r g , A. S t i m u l a t i o n o f r a t m e d i a l o r s u l c a l p r e f r o n t a l c o r t e x d u r i n g p a s s i v e a v o i d a n c e l e a r n i n g s e l e c t i v e l y i n f l u e n c e s r e t e n t i o n p e r f o r m a n c e . B r a i n R e s e a r c h , 1976, 243-259. S c h w a r t z , M., and T e i t e l b a u m , P. D i s s o c i a t i o n between l e a r n i n g and remembering i n r a t s w i t h l e s i o n s i n t h e l a t e r a l h y pothalamus. J o u r n a l o f C o m p a r a t i v e and  P h y s i o l o g i c a l P s y c h o l o g y , 1974, 87, 384-398. 63 Shinkman, P.G., and Kaufman, K.P. P o s t t r i a l h i p p o c a m p a l s t i m u l a t i o n and CER a c q u i s i t i o n i n t h e r a t . J o u r n a l o f C o m p a r a t i v e and P h y s i o l o g i c a l  P s y c h o l o g y , 1972, 80, 283-292. S i e g e l , J . L . E f f e c t o f m e d i a l s e p t a l l e s i o n s on c o n d i t i o n e d t a s t e a v e r s i o n i n t h e r a t . P h y s i o l o g y and B e h a v i o r , 1976, \17_, 761-765. S m i t h , J.C., and R o l l , D.L. T r a c e c o n d i t i o n i n g w i t h X - r a y s as an a v e r s i v e s t i m u l u s . Psychonomic S c i e n c e , 1967, 9_, 11-12. T e i t e l b a u m , P., and E p s t e i n , A.N. The l a t e r a l h y p o t h a l a m i c syndrome: R e c o v e r y of f e e d i n g and d r i n k i n g a f t e r l a t e r a l h y p o t h a l a m i c l e s i o n s . P s y c h o l o g i c a l  Review, 1962, 69, 74-90. Wendt, R., and A l b e - F e s s a r d , D. S e n s o r y r e s p o n s e s o f t h e amygdala w i t h s p e c i a l r e f e r e n c e t o s e m a t i c a f f e r e n t pathways. I n P h y s i o l o g i e de 1 ] h i p p o - camp e. P a r i s : C e n t r e N a t i o n a l de l a R echerche S c i e n t i f i q u e , 1962. Pp. 171-200. W i l b u r n , M.W., and K e s n e r , R.P. D i f f e r e n t i a l a m n e s t i c e f f e c t s p r o duced by e l e c t r i c a l s t i m u l a t i o n o f t h e c a u d a t e n u c l e u s and n o n s p e c i f i c t h a l a m i c s y s t e m s . E x p e r i m e n t a l N e u r o l o g y , 1972, _34_, 45-50. W i l c o x o n , H.C., D r a g i o n , W.B., and K r a i , P.A. I l l n e s s - i n d u c e d a v e r s i o n s i n r a t s and q u a i l : R e l a t i v e s a l i e n c e of v i s u a l and g u s t a t o r y c u e s . S c i e n c e , 1971, 171, 826-828. Wyers, E . J . , and D eadwyler, S.A. D u r a t i o n and n a t u r e o f r e t r o g r a d e amnesia produced by s t i m u l a t i o n o f c a u d a t e n u c l e u s . P h y s i o l o g y and B e h a v i o r , 1971, 6, 97-103. Wyers, E . J . , Deadwyler, S.A., H i r a s u n a , N., and Montgomery, D. P a s s i v e a v o i d a n c e r e t e n t i o n and r e t r o a c t i v e c a u d a t e s t i m u l a t i o n . P h y s i o l o g y and  B e h a v i o r , 1973, 11, 809-819. Wyers, E . J . , Peeke, H.V.S., W i l l i s t o n , J.S., and H e r z , M.J. R e t r o a c t i v e i m p a i rment o f p a s s i v e a v o i d a n c e l e a r n i n g by s t i m u l a t i o n o f t h e c a u d a t e n u c l e u s . E x p e r i m e n t a l N e u r o l o g y , 1968, 22_, 350-366. 

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}]}"
                            data-media="{[{embed.selectedMedia}]}"
                            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:
https://iiif.library.ubc.ca/presentation/dsp.831.1-0094431/manifest

Comment

Related Items