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Escape from rewarding brain stimulation of dorsal brainstem and hypothalamus
Phystology and Behavior, Vol 11, pp 589-591 Brain Research Publlcatmns Inc , 1973 Prmted m the U S A
BRIEF COMMUNICATION Escape from Rewarding Brain Stimulation of Dorsal Brainstem and Hypothalamus' S O L O M O N S. S T E I N E R , R I C H A R D J. BODNAR, ROBERT F A C K E R M A N N A N D S T E V E N J E L L M A N
Department o/Psychology, City College o f the Czty Umverstty o f New York, New York, New York 10031
(Received 13 April 1973) STEINER, S. S , R. J BODNAR, R F. ACKERMANN AND S J. ELLMAN Escapefrorn rewarding brain sttmulatton of dorsal bramstem and hypothalamus PHYSIOL BEHAV 11(4)589-591, 1973 kach ot 9 albino rats had two bipolar electrodes aimed at lateral hypothalamic and either of two dorsal bralnstem (dorsal raphe or locus coeruleus) snes Every rat bar-pressed for stimulation at each electrode Then, each animal learned to treadle-press to escape from passive electrical stimulation at each elctrode site All ammals learned to escape from first dorsal bralnstem and then lateral hypothalamIc stimulation at current lntensmes which also supported self-StmlulatIon behavmr Ammals appeared hyperactive under lateral hypothalamlc sUmulatlon (acUve or passive), but not under dorsal bramstem stmlulatlon Electrical brain st~mulatmn
Escape
Dorsal bramstem
Lateral hypothalamus
Locus coeruleus
dorsal madbram and h m d b r a m sites which have been s h o w n to sustain self-stamulataon b e h a v m r Specafacally, the p r o t o col of t h e e x p e r i m e n t was to i m p l a n t rats w i t h a pair of e l e c t r o d e s , one m the lateral h y p o t h a l a m u s , the o t h e r in the dorsal b r a l n s t e m (dorsal raphe or locus coeruleus), t h e n to d e m o n s t r a t e s e l f - s t l m u l a t m n m b o t h e l e c t r o d e sites for all animals, finally, to test for escape f r o m passive stamulatlon of the dorsal b r a l n s t e m sites The p u r p o s e o f i m p l a n t i n g e l e c t r o d e s an b o t h the dorsal b r a m s t e m and the h y p o t h a l a m u s was to d e m o n s t r a t e that a p a m c u l a r animal was capable o f acquiring an escape res p o n s e m the event that it failed to escape from dorsal bralnstem stimulation.
OLDS and M d n e r [7] d e m o n s t r a t e d t h a t rats wall w o r k to o b t a i n electrical s t i m u l a t i o n o f various f o r e b r a m subcortacal areas. Margules [6] f o u n d t h a t rats wall w o r k to o b t a i n electrical s t i m u l a t i o n o f the dorsal r a p h e nucleus, a mldb r a m s t r u c t u r e Farber, SteIner and Ellman [5] r e p o r t e d s e l f - s t i m u l a t m n b e h a v i o r an rats for s t l m u l a t m n d e h v e r e d to the locus coeruleus, a handbraxn sate. B o w e r and Mdler [2] f o u n d t h a t rats escape f r o m , but d o n o t avoid, electrical stamulation o f m a n y h y p o t h a l a m a c sates. T h e y p o s t u l a t e d that the onset o f electrical brain s t i m u l a t i o n is positively r e i n f o r c i n g but t h a t , if c o n t i n u e d , the stamulatlon b e c o m e s averslve over time. T h e r e f o r e , rats p e r f o r m tasks to terminate the stlmulataon, but wall n o t p e r f o r m tasks w h i c h preclude the o n s e t of stamulation (i.e., avoidance) A f t e r investigating the h y p o t h a l a m a c area, B o w e r and Miller c o n c l u d e d that stamulatlon o f the a n t e r i o r h y p o t h a l a m u s ehclts escape r e s p o n d i n g , b u t that p o s t e r i o r h y p o t h a l a m l c s t i m u l a t i o n does n o t However, escape f r o m posteraor h y p o t h a l a m a c stamulatlon was d e m o n s t r a t e d b y Beer and Sterner [1] C o o p e r and Taylor [3] indacated that rats will b o t h selfstamulate and escape f r o m a n t e r i o r mxdbraln perlventracular stamulataon Stelner et al [10] d e m o n s t r a t e d that rats will escape f r o m electrical brain stxmulatmn, even w h e n the stamulatmn as d e h v e r e d to the same sate and at the same p a r a m e t e r s that the animal had previously elected to receive. The p u r p o s e o f this e x p e r i m e n t was to test w h e t h e r rats wall escape f r o m electrical brain s t i m u l a t i o n an various
METHOD Nine H o l t z m a n Sprague-Dawley rats (375 425 g) were a n e s t h e t i z e d ( E q m t h e s l n , 1 . 0 0 - 1 . 5 0 cc) and i m p l a n t e d with t w o stainless steel bipolar e l e c t r o d e s w h i c h were 0 5 m m wide at their widest e x t e n t , and c o m p l e t e l y insulated e x c e p t at the tips In each animal, e l e c t r o d e s were aimed at lateral h y p o t h a l a m l c and either o f t w o dorsal b r a m s t e m sates dorsal raphe nucleus or locus coeruleus A f t e r recovery f r o m surgery ( 10 days), each a m m a l was placed in a Skinner b o x and shaped to bar press R e i n f o r c e m e n t s were trams of electric c u r r e n t (60 c/s sane, 0 5 sec d u r a t i o n ) passed t h r o u g h one o f the animal's two e l e c t r o d e s Current was c o n t i n u o u s l y m o n i t o r e d on a d l f f e r e n t m l i n p u t
Supported by NIMH Grant No 18908 589
590
STEINER, BODNAR, ACKERMANN AND ELLMAN
oscilloscope and was v a n e d f r o m 0 210 u A a c c o r d i n g to the d e m a n d s of the e x p e r i m e n t All nine a n u n a l s s h o w e d stable bar-press b e h a v i o r for electrical s h m u l a t m n o n a cont m u o u s r e i n f o r c e m e n t schedule t h r o u g h first dorsal brainstein and t h e n lateral h y p o t h a l a m l c electrodes (dorsal brainstem was always tested first) Animals were t h e n t r a i n e d to escape from passive b r a i n s t l m u l a t m n m a d i f f e r e n t S k i n n e r b o x The o n s e t of a stream of elctr:cal t r a m s (60 c/s, 0 5 sec d u r a t i o n , 0 5 sec m t e r t r a m interval) d e h v e r e d t h r o u g h o n e of the a n i m a l ' s t w o electrodes, m a r k e d the b e g i n n i n g o f the first trial S t i m u l a t i o n c o n t i n u e d until e i t h e r the a m m a l depressed a treadle, or 101 t r a m s had b e e n delivered. A f t e r a 15-sec lntertrml interval, the s t l m u l a t m n was a u t o m a t i c a l l y relnitlated and the p r o c e d u r e r e p e a t e d successively until a b l o c k of 10 trials was r u n All changes in c u r r e n t i n t e n s i t i e s were m a d e b e t w e e n the 10-trial blocks F o r each e l e c t r o d e site. an m t e n s t t y was c h o s e n w h i c h would sustain o p t i m a l escape b e h a v i o r , in some cases, these l n t e n s m e s were lower t h a n s e l f - s t l m u l a t m n t h r e s h o l d s A f t e r the animal learned to escape from passive stimulation t h r o u g h its dorsal b r a l n s t e m e l e c t r o d e , 50 escape trials per day were r u n for six c o n s e c u t i v e days The first b l o c k of I0 trials was a w a r m - u p period In the s u b s e q u e n t 4 blocks of trials l l 0 t r i a l s / b l o c k ) , the c u r r e n t i n t e n s i t y altern a t e d b e t w e e n 0 u A ( n o - s t l m u l a t m n c o n d i t i o n ) and the ammal's preselected escape i n t e n s i t y ( s t x m u l a t m n c o n d l t l o n l m an ABBA s e q u e n c e , this s e q u e n c e was c o u n t e r b a l a n c e d across days T o reduce c o n t a m i n a t i o n *roln possible e x c i t a t o r y effects of s t i m u l a t i o n , the e x p e r i m e n t e r disallowed all b u t discrete escape r e s p o n d i n g tdepresss:on of the treadle w i t h a f o r e p a w ) during s t i m u l a t i o n c o n d i t i o n s , this practice was n o t applied during n o - s t i m u l a t i o n c o n d l h o n s , d u r i n g w h i c h treadle depression b y any m e a n s t e r m i n a t e d the trial In similar fashion, the animal was t h e n s h a p e d to escape from lateral h y p o t h a l a m l c s t i m u l a t i o n and s u b s e q u e n t l y run t h r o u g h 50 escape trials per day for 6 c o n s e c u t i v e days Every a m m a l was trained to escape f r o m passive dorsal b r a l n s t e m s t l i n u l a t i o n before it was i n t r o d u c e d to passive lateral h y p o t h a l a m : c s t i m u l a t i o n , this was d o n e to insure t h a t carryover effects, :f any, would a p p e a r m the lateral h y p o t h a l a m l c data, leaving dorsal m l d b r a i n escape data uncontammated After the animal c o m p l e t e d b o t h 6-day escape sequences, c u r r e n t intensities w h i c h would s u p p o r t b o t h s e l f - s t : m u l a t m n and escape b e h a v i o r m each e l e c t r o d e site were selected T h e n . in each of t w o c o n s e c u t i v e days, the selected intenslt:r served h r s t as negative r e i n f o r c e r in 20 escape trials, t h e n as a positive r e i n f o r c e r m 20 m i n u t e - l o n g self-st~mulatmn trials F o r each e l e c t r o d e site m each a m m a l , a m e a n escape latency over 120 trials m the s t i m u l a t i o n c o n d i t i o n was calculated and c o m p a r e d to the c o r r e s p o n d i n g m e a n escape latency in the n o - s t i m u l a t i o n c o n d i t i o n U p o n c o m p l e t i o n of the e x p e n m e n t , animals were sacrificed and e l e c t r o d e p l a c e m e n t s verified t h r o u g h r o u t i n e neurohistological procedures RESULTS
In each e l e c t r o d e site in every animal, the m e a n escape l a t e n c y was significantly s h o r t e r u n d e r the s t i m u l a t i o n cond i t m n t h a n u n d e r the n o - s t i m u l a t i o n c o n d i t i o n (Table 1) Sign tests were p e r f o r m e d on each and every a n i m a l ' s data,
and all were significant at the 17-<0 01 level F o r each e l e c t r o d e site in every animal, t h e r e was at least one c u r r e n t i n t e n s i t y at w h i c h the a m m a l would b o t h escape and s e l f - s h m u l a t e lTable 1 I In all dorsal b r a l n s t e m electrode sites, b o t h active selfs t i m u l a t i o n and passive escape s t i m u l a t i o n resulted m n o n affectlve r e s p o n d i n g . U n d e r these c o n d i t i o n s , r e s p o n d i n g t e n d e d to be discrete On the o t h e r h a n d , h y p o t h a l a i m c s t l m u l a t m n , w h e t h e r a d m i n i s t e r e d passively or actively as a result of bar pressing, f r e q u e n t l y led to behavioral arousal. Animals b e c a m e h y p e r a c t i v e , and u n d e r the influence o f p r o l o n g e d s t i m u l a t i o n in escape c o n d i t i o n s , displayed compulsive sniffing b e h a v i o r which c o m p e t e d with treadlepressing b e h a v i o r Thus, responses u n d e r c o n d i t i o n s of lateral h y p o t h a l a m l c s t i m u l a t i o n t e n d e d to be less discrete t h a n t h o s e to dorsal b r a m s t e m s t i m u l a t i o n F u r t h e r m o r e , a m m a t s s h o w e d h t t l e evidence of t r a n s f e r of learning b e t w e e n sites After the animals had r u n at least 200 escape trials for dorsal b r a l n s t e i n s t l m u l a t m n , t h e y had to be r e s h a p e d b e f o r e they w o u l d escape from lateral h y p o thalam:c sllmulatlon DISCUSSION
A n u m b e r of t h e o r i s t s have suggested the existence of several distinct n e u r o a n a t o m l c a l systems to m e d i a t e dascrete aspects o f o p e r a n t b e h a v i o r D e u t s c h [4] p o s t u l a t e d one system for drive arousal, and a n o t h e r for positive reinf o r c e m e n t Bower and Miller [ 21 and Olds [8,9] suggested a separate system for negative r e i n f o r c e m e n t These h y p o theses imply the possibility of discrete n e u r o a n a t o m l c a l areas in which electrical s t i m u l a t i o n s u p p o r t s selfs t l m u l a t m n b e h a v i o r , b u t n o t escape b e h a v i o r In o t h e r words, there s h o u l d be areas of pure p o s m v e r e i n f o r c e m e n t Thus far, all brain areas w h i c h have b e e n f o u n d to s u p p o r t s e l f - s t l m u l a h o n b e h a v i o r eventually have b e e n f o u n d to s u p p o r t escape b e h a v i o r also We e n t e r e d this s t u d y w i t h t h e idea t h a t some dorsal b r a i n s t e m areas m i g h t s u p p o r t only s e l f - s t i m u l a t i o n b e h a v i o r , b u t , as o u r data s h o w , dorsal braxnstem e l e c t n c a l s t i m u l a t i o n s u p p o r t s escape b e h a w o r as well T h u s , the pure positive r e i n f o r c e m e n t area r e m a i n s undiscovered T h e r e is n o q u e s t i o n t h a t rats escape f r o m dorsal brains t e m s t i m u l a t i o n Each animal, each day, had l o w e r escape latencles for s t i m u l a t i o n t h a n for n o - s t i m u l a t i o n c o n d i t i o n s . These data had little v a n a b l h t y and were r e h a b l e n o t o n l y across days, b u t also from b l o c k to b l o c k w~thln days, and even from trial to trial w i t h i n blocks To reduce the effect of n o n s p e c i f l c h y p e r a c t i v i t y ind u c e d by s t i m u l a t m n , all b u t discrete responses were disallowed during s t i m u l a t i o n c o n d i t i o n s , d u r i n g no*stlmulatlon c o n d i t i o n s , a treadle press m a d e b y any m e a n s termin a t e d a trial This practice t e n d e d to increase escape latencIes u n d e r s t i m u l a t i o n c o n & t l o n s , d r a w i n g t h e m closer to n o - s t i m u l a t i o n latencles In splte ot this, s t i m u l a t i o n escape latencles were m u c h s h o r t e r t h a n n o - s t ~ m u l a t m n latencies F u r t h e r m o r e , s t i m u l a t i o n - i n d u c e d h y p e r a c h v l t y , observed only for lateral h y p o t h a l a m m s t i m u l a t i o n , was f r e q u e n t l y a c c o m p a n i e d by compulsive sniffing b e h a v i o r i n c o m p a t i b l e with treadle-press b e h a v i o r This also t e n d e d to increase escape latencies The o b s e r v a t i o n tha! s t i m u l a t l o n - l n d u c e d h y p e r a c t i v i t y characterized only lateral h y p o t h a l a m i c s t : m u l a t m n is i m p o r t a n t because it suggests t h a t s t i i n u l a t l o n at these two sites was e x p e r i e n t i a l l y d i f f e r e n t C o r r o b o r a t i n g this was
ESCAPE FROM REWARDING
BRAINSTEM
STIMULATION
591
TABLE
1
COMPARISON OF MEAN ESCAPE LATENCY (SEC) BETWEEN DORSAL BRAINSTEM AND L A T E R A L HYPOTHALAMIC SITES
ELECTRODE SITE Dorsal Bramstem Stmlulus Intensity (tzA)
X Escape Latency (See)
Zero Control Latency (See)
IE
29
7 43
70 4
97C
50
12 7
96("
50 78*
98C
100C
ANIMAL
91'
Lateral H y p o t h a l a m u s Stmlulus Intensity (~tA)
X Escape Latency (Sec)
Zero Control Latency (Sec)
mldbram DLF
28 49*
24 2 18 4
69 6 82 3
lateral hypothalanms
76 4
dorsal thalamus
32
22 8
86 9
caudate nucleus
8 03 15 0
81 5 52 5
undbraln DLI,
182
36 3
89 3
lateral hypothalamus
57
13 42
77 0
oculomotor nucleus
29 35*
9 I 5 6
52 3 47 6
zona mserta
21
76
81 4
mJdbram DLI"
70
15 0
76 3
lateral hypothalamus
18 7 22 3
92 5 88 3
sub-coerulean tract
98
18 9
97 3
lateral hypothalamus
20 23 ~
Actual Electrode Placement
Actual Electrode Placement
131'
98
8 3
59 3
tNgemmal mescncephahc nucl
84
14 9
73 4
lateral hypothalamus
12F
212
22 8
88 7
no h~stology
98
11 7
90 1
no lustology
14E
212
10 8
54 7
sub-coerulean tract
57
13 7
86 5
lateral hypothalamus
NOTE
In cases where two mtensHles appear for an ammal at a site, tile unstarred intensity Is that wluch was used during tile 6-day escape trials The starred intensity Js that which supported both escape and self-stmlulatlon behaviors
t h e a m m a l s ' a p p a r e n t d i f f i c u l t y m t r a n s f e r r i n g e s c a p e responding from dorsal bramstem to lateral hypothalamlc shmulahon, suggesting that the ammals' phenomenal exper-
lences under the mfluence of dorsal bramstem electrical s t i m u l a t i o n are q u a h t a t l v e l y d i f f e r e n t f r o m t h o s e u n d e r lateral hypothalamlc stimulahon
REFERENCES l
2
3 4
5
Beer, B and S. Sterner An analysis of the ambivalent properties of electrical brain stimulation. Paper presented at the Psychononucs Society, Chicago, llhnols, 1965. Bower, G H. and N E Miller Rewarding and p u m s h m g effects from stimulating the same place m the rat's brain J comp phystol Psyehol 51: 6 6 9 - 6 7 4 , 2958 Cooper, R. M. and L H Taylor Thalamlc reticular system and central grey sell'-shmulatlon Science 1 5 6 : 1 0 2 203, 1967 Deutsch, J A , ('. I. Howarth, G G Ball and D Deutsch Threshold dffferentmtlon o f drive and reward m tile Olds effect Nature 196: 699- 700, 2962 Farber, J., S Stelner and S. J Ellman The pons as an electrical self-stimulation site Psyehophystology 9: 105, 1972. (Abstract)
6
Margules, D L Noradrenerglc rather than serotonerglc basis ol reward m the dorsal t e g m e n t u m J comp pto,stol Psvchol 67: 32 35, 1969 7 Olds, J and P Mdner Positive r e m l o r c e m e n t produced by electrical stmlulatlon o f septal area and other regions ol the rat brain J comp phystol Psychol 4 7 : 4 1 9 429, 1954 8 OIds, J A p r e h m m a r y m a p p m g o f e l e c m c a l r e m l o r c m g e t l e c t s in the rat brain J comp phystol Psvchol 49: 281, 1956 9. Olds, J Self-stnnlatlon of tile brain Science 127: 315, 2958 IO Sterner, S., B Beer and M Schaffcr Escape from sell-produce,' rates of b r a l n s t l m u l a t l o n Scwnce 1 6 3 : 9 0 92, 1969
BRIEF COMMUNICATION Escape from Rewarding Brain Stimulation of Dorsal Brainstem and Hypothalamus' S O L O M O N S. S T E I N E R , R I C H A R D J. BODNAR, ROBERT F A C K E R M A N N A N D S T E V E N J E L L M A N
Department o/Psychology, City College o f the Czty Umverstty o f New York, New York, New York 10031
(Received 13 April 1973) STEINER, S. S , R. J BODNAR, R F. ACKERMANN AND S J. ELLMAN Escapefrorn rewarding brain sttmulatton of dorsal bramstem and hypothalamus PHYSIOL BEHAV 11(4)589-591, 1973 kach ot 9 albino rats had two bipolar electrodes aimed at lateral hypothalamic and either of two dorsal bralnstem (dorsal raphe or locus coeruleus) snes Every rat bar-pressed for stimulation at each electrode Then, each animal learned to treadle-press to escape from passive electrical stimulation at each elctrode site All ammals learned to escape from first dorsal bralnstem and then lateral hypothalamIc stimulation at current lntensmes which also supported self-StmlulatIon behavmr Ammals appeared hyperactive under lateral hypothalamlc sUmulatlon (acUve or passive), but not under dorsal bramstem stmlulatlon Electrical brain st~mulatmn
Escape
Dorsal bramstem
Lateral hypothalamus
Locus coeruleus
dorsal madbram and h m d b r a m sites which have been s h o w n to sustain self-stamulataon b e h a v m r Specafacally, the p r o t o col of t h e e x p e r i m e n t was to i m p l a n t rats w i t h a pair of e l e c t r o d e s , one m the lateral h y p o t h a l a m u s , the o t h e r in the dorsal b r a l n s t e m (dorsal raphe or locus coeruleus), t h e n to d e m o n s t r a t e s e l f - s t l m u l a t m n m b o t h e l e c t r o d e sites for all animals, finally, to test for escape f r o m passive stamulatlon of the dorsal b r a l n s t e m sites The p u r p o s e o f i m p l a n t i n g e l e c t r o d e s an b o t h the dorsal b r a m s t e m and the h y p o t h a l a m u s was to d e m o n s t r a t e that a p a m c u l a r animal was capable o f acquiring an escape res p o n s e m the event that it failed to escape from dorsal bralnstem stimulation.
OLDS and M d n e r [7] d e m o n s t r a t e d t h a t rats wall w o r k to o b t a i n electrical s t i m u l a t i o n o f various f o r e b r a m subcortacal areas. Margules [6] f o u n d t h a t rats wall w o r k to o b t a i n electrical s t i m u l a t i o n o f the dorsal r a p h e nucleus, a mldb r a m s t r u c t u r e Farber, SteIner and Ellman [5] r e p o r t e d s e l f - s t i m u l a t m n b e h a v i o r an rats for s t l m u l a t m n d e h v e r e d to the locus coeruleus, a handbraxn sate. B o w e r and Mdler [2] f o u n d t h a t rats escape f r o m , but d o n o t avoid, electrical stamulation o f m a n y h y p o t h a l a m a c sates. T h e y p o s t u l a t e d that the onset o f electrical brain s t i m u l a t i o n is positively r e i n f o r c i n g but t h a t , if c o n t i n u e d , the stamulatlon b e c o m e s averslve over time. T h e r e f o r e , rats p e r f o r m tasks to terminate the stlmulataon, but wall n o t p e r f o r m tasks w h i c h preclude the o n s e t of stamulation (i.e., avoidance) A f t e r investigating the h y p o t h a l a m a c area, B o w e r and Miller c o n c l u d e d that stamulatlon o f the a n t e r i o r h y p o t h a l a m u s ehclts escape r e s p o n d i n g , b u t that p o s t e r i o r h y p o t h a l a m l c s t i m u l a t i o n does n o t However, escape f r o m posteraor h y p o t h a l a m a c stamulatlon was d e m o n s t r a t e d b y Beer and Sterner [1] C o o p e r and Taylor [3] indacated that rats will b o t h selfstamulate and escape f r o m a n t e r i o r mxdbraln perlventracular stamulataon Stelner et al [10] d e m o n s t r a t e d that rats will escape f r o m electrical brain stxmulatmn, even w h e n the stamulatmn as d e h v e r e d to the same sate and at the same p a r a m e t e r s that the animal had previously elected to receive. The p u r p o s e o f this e x p e r i m e n t was to test w h e t h e r rats wall escape f r o m electrical brain s t i m u l a t i o n an various
METHOD Nine H o l t z m a n Sprague-Dawley rats (375 425 g) were a n e s t h e t i z e d ( E q m t h e s l n , 1 . 0 0 - 1 . 5 0 cc) and i m p l a n t e d with t w o stainless steel bipolar e l e c t r o d e s w h i c h were 0 5 m m wide at their widest e x t e n t , and c o m p l e t e l y insulated e x c e p t at the tips In each animal, e l e c t r o d e s were aimed at lateral h y p o t h a l a m l c and either o f t w o dorsal b r a m s t e m sates dorsal raphe nucleus or locus coeruleus A f t e r recovery f r o m surgery ( 10 days), each a m m a l was placed in a Skinner b o x and shaped to bar press R e i n f o r c e m e n t s were trams of electric c u r r e n t (60 c/s sane, 0 5 sec d u r a t i o n ) passed t h r o u g h one o f the animal's two e l e c t r o d e s Current was c o n t i n u o u s l y m o n i t o r e d on a d l f f e r e n t m l i n p u t
Supported by NIMH Grant No 18908 589
590
STEINER, BODNAR, ACKERMANN AND ELLMAN
oscilloscope and was v a n e d f r o m 0 210 u A a c c o r d i n g to the d e m a n d s of the e x p e r i m e n t All nine a n u n a l s s h o w e d stable bar-press b e h a v i o r for electrical s h m u l a t m n o n a cont m u o u s r e i n f o r c e m e n t schedule t h r o u g h first dorsal brainstein and t h e n lateral h y p o t h a l a m l c electrodes (dorsal brainstem was always tested first) Animals were t h e n t r a i n e d to escape from passive b r a i n s t l m u l a t m n m a d i f f e r e n t S k i n n e r b o x The o n s e t of a stream of elctr:cal t r a m s (60 c/s, 0 5 sec d u r a t i o n , 0 5 sec m t e r t r a m interval) d e h v e r e d t h r o u g h o n e of the a n i m a l ' s t w o electrodes, m a r k e d the b e g i n n i n g o f the first trial S t i m u l a t i o n c o n t i n u e d until e i t h e r the a m m a l depressed a treadle, or 101 t r a m s had b e e n delivered. A f t e r a 15-sec lntertrml interval, the s t l m u l a t m n was a u t o m a t i c a l l y relnitlated and the p r o c e d u r e r e p e a t e d successively until a b l o c k of 10 trials was r u n All changes in c u r r e n t i n t e n s i t i e s were m a d e b e t w e e n the 10-trial blocks F o r each e l e c t r o d e site. an m t e n s t t y was c h o s e n w h i c h would sustain o p t i m a l escape b e h a v i o r , in some cases, these l n t e n s m e s were lower t h a n s e l f - s t l m u l a t m n t h r e s h o l d s A f t e r the animal learned to escape from passive stimulation t h r o u g h its dorsal b r a l n s t e m e l e c t r o d e , 50 escape trials per day were r u n for six c o n s e c u t i v e days The first b l o c k of I0 trials was a w a r m - u p period In the s u b s e q u e n t 4 blocks of trials l l 0 t r i a l s / b l o c k ) , the c u r r e n t i n t e n s i t y altern a t e d b e t w e e n 0 u A ( n o - s t l m u l a t m n c o n d i t i o n ) and the ammal's preselected escape i n t e n s i t y ( s t x m u l a t m n c o n d l t l o n l m an ABBA s e q u e n c e , this s e q u e n c e was c o u n t e r b a l a n c e d across days T o reduce c o n t a m i n a t i o n *roln possible e x c i t a t o r y effects of s t i m u l a t i o n , the e x p e r i m e n t e r disallowed all b u t discrete escape r e s p o n d i n g tdepresss:on of the treadle w i t h a f o r e p a w ) during s t i m u l a t i o n c o n d i t i o n s , this practice was n o t applied during n o - s t i m u l a t i o n c o n d l h o n s , d u r i n g w h i c h treadle depression b y any m e a n s t e r m i n a t e d the trial In similar fashion, the animal was t h e n s h a p e d to escape from lateral h y p o t h a l a m l c s t i m u l a t i o n and s u b s e q u e n t l y run t h r o u g h 50 escape trials per day for 6 c o n s e c u t i v e days Every a m m a l was trained to escape f r o m passive dorsal b r a l n s t e m s t l i n u l a t i o n before it was i n t r o d u c e d to passive lateral h y p o t h a l a m : c s t i m u l a t i o n , this was d o n e to insure t h a t carryover effects, :f any, would a p p e a r m the lateral h y p o t h a l a m l c data, leaving dorsal m l d b r a i n escape data uncontammated After the animal c o m p l e t e d b o t h 6-day escape sequences, c u r r e n t intensities w h i c h would s u p p o r t b o t h s e l f - s t : m u l a t m n and escape b e h a v i o r m each e l e c t r o d e site were selected T h e n . in each of t w o c o n s e c u t i v e days, the selected intenslt:r served h r s t as negative r e i n f o r c e r in 20 escape trials, t h e n as a positive r e i n f o r c e r m 20 m i n u t e - l o n g self-st~mulatmn trials F o r each e l e c t r o d e site m each a m m a l , a m e a n escape latency over 120 trials m the s t i m u l a t i o n c o n d i t i o n was calculated and c o m p a r e d to the c o r r e s p o n d i n g m e a n escape latency in the n o - s t i m u l a t i o n c o n d i t i o n U p o n c o m p l e t i o n of the e x p e n m e n t , animals were sacrificed and e l e c t r o d e p l a c e m e n t s verified t h r o u g h r o u t i n e neurohistological procedures RESULTS
In each e l e c t r o d e site in every animal, the m e a n escape l a t e n c y was significantly s h o r t e r u n d e r the s t i m u l a t i o n cond i t m n t h a n u n d e r the n o - s t i m u l a t i o n c o n d i t i o n (Table 1) Sign tests were p e r f o r m e d on each and every a n i m a l ' s data,
and all were significant at the 17-<0 01 level F o r each e l e c t r o d e site in every animal, t h e r e was at least one c u r r e n t i n t e n s i t y at w h i c h the a m m a l would b o t h escape and s e l f - s h m u l a t e lTable 1 I In all dorsal b r a l n s t e m electrode sites, b o t h active selfs t i m u l a t i o n and passive escape s t i m u l a t i o n resulted m n o n affectlve r e s p o n d i n g . U n d e r these c o n d i t i o n s , r e s p o n d i n g t e n d e d to be discrete On the o t h e r h a n d , h y p o t h a l a i m c s t l m u l a t m n , w h e t h e r a d m i n i s t e r e d passively or actively as a result of bar pressing, f r e q u e n t l y led to behavioral arousal. Animals b e c a m e h y p e r a c t i v e , and u n d e r the influence o f p r o l o n g e d s t i m u l a t i o n in escape c o n d i t i o n s , displayed compulsive sniffing b e h a v i o r which c o m p e t e d with treadlepressing b e h a v i o r Thus, responses u n d e r c o n d i t i o n s of lateral h y p o t h a l a m l c s t i m u l a t i o n t e n d e d to be less discrete t h a n t h o s e to dorsal b r a m s t e m s t i m u l a t i o n F u r t h e r m o r e , a m m a t s s h o w e d h t t l e evidence of t r a n s f e r of learning b e t w e e n sites After the animals had r u n at least 200 escape trials for dorsal b r a l n s t e i n s t l m u l a t m n , t h e y had to be r e s h a p e d b e f o r e they w o u l d escape from lateral h y p o thalam:c sllmulatlon DISCUSSION
A n u m b e r of t h e o r i s t s have suggested the existence of several distinct n e u r o a n a t o m l c a l systems to m e d i a t e dascrete aspects o f o p e r a n t b e h a v i o r D e u t s c h [4] p o s t u l a t e d one system for drive arousal, and a n o t h e r for positive reinf o r c e m e n t Bower and Miller [ 21 and Olds [8,9] suggested a separate system for negative r e i n f o r c e m e n t These h y p o theses imply the possibility of discrete n e u r o a n a t o m l c a l areas in which electrical s t i m u l a t i o n s u p p o r t s selfs t l m u l a t m n b e h a v i o r , b u t n o t escape b e h a v i o r In o t h e r words, there s h o u l d be areas of pure p o s m v e r e i n f o r c e m e n t Thus far, all brain areas w h i c h have b e e n f o u n d to s u p p o r t s e l f - s t l m u l a h o n b e h a v i o r eventually have b e e n f o u n d to s u p p o r t escape b e h a v i o r also We e n t e r e d this s t u d y w i t h t h e idea t h a t some dorsal b r a i n s t e m areas m i g h t s u p p o r t only s e l f - s t i m u l a t i o n b e h a v i o r , b u t , as o u r data s h o w , dorsal braxnstem e l e c t n c a l s t i m u l a t i o n s u p p o r t s escape b e h a w o r as well T h u s , the pure positive r e i n f o r c e m e n t area r e m a i n s undiscovered T h e r e is n o q u e s t i o n t h a t rats escape f r o m dorsal brains t e m s t i m u l a t i o n Each animal, each day, had l o w e r escape latencles for s t i m u l a t i o n t h a n for n o - s t i m u l a t i o n c o n d i t i o n s . These data had little v a n a b l h t y and were r e h a b l e n o t o n l y across days, b u t also from b l o c k to b l o c k w~thln days, and even from trial to trial w i t h i n blocks To reduce the effect of n o n s p e c i f l c h y p e r a c t i v i t y ind u c e d by s t i m u l a t m n , all b u t discrete responses were disallowed during s t i m u l a t i o n c o n d i t i o n s , d u r i n g no*stlmulatlon c o n d i t i o n s , a treadle press m a d e b y any m e a n s termin a t e d a trial This practice t e n d e d to increase escape latencIes u n d e r s t i m u l a t i o n c o n & t l o n s , d r a w i n g t h e m closer to n o - s t i m u l a t i o n latencles In splte ot this, s t i m u l a t i o n escape latencles were m u c h s h o r t e r t h a n n o - s t ~ m u l a t m n latencies F u r t h e r m o r e , s t i m u l a t i o n - i n d u c e d h y p e r a c h v l t y , observed only for lateral h y p o t h a l a m m s t i m u l a t i o n , was f r e q u e n t l y a c c o m p a n i e d by compulsive sniffing b e h a v i o r i n c o m p a t i b l e with treadle-press b e h a v i o r This also t e n d e d to increase escape latencies The o b s e r v a t i o n tha! s t i m u l a t l o n - l n d u c e d h y p e r a c t i v i t y characterized only lateral h y p o t h a l a m i c s t : m u l a t m n is i m p o r t a n t because it suggests t h a t s t i i n u l a t l o n at these two sites was e x p e r i e n t i a l l y d i f f e r e n t C o r r o b o r a t i n g this was
ESCAPE FROM REWARDING
BRAINSTEM
STIMULATION
591
TABLE
1
COMPARISON OF MEAN ESCAPE LATENCY (SEC) BETWEEN DORSAL BRAINSTEM AND L A T E R A L HYPOTHALAMIC SITES
ELECTRODE SITE Dorsal Bramstem Stmlulus Intensity (tzA)
X Escape Latency (See)
Zero Control Latency (See)
IE
29
7 43
70 4
97C
50
12 7
96("
50 78*
98C
100C
ANIMAL
91'
Lateral H y p o t h a l a m u s Stmlulus Intensity (~tA)
X Escape Latency (Sec)
Zero Control Latency (Sec)
mldbram DLF
28 49*
24 2 18 4
69 6 82 3
lateral hypothalanms
76 4
dorsal thalamus
32
22 8
86 9
caudate nucleus
8 03 15 0
81 5 52 5
undbraln DLI,
182
36 3
89 3
lateral hypothalamus
57
13 42
77 0
oculomotor nucleus
29 35*
9 I 5 6
52 3 47 6
zona mserta
21
76
81 4
mJdbram DLI"
70
15 0
76 3
lateral hypothalamus
18 7 22 3
92 5 88 3
sub-coerulean tract
98
18 9
97 3
lateral hypothalamus
20 23 ~
Actual Electrode Placement
Actual Electrode Placement
131'
98
8 3
59 3
tNgemmal mescncephahc nucl
84
14 9
73 4
lateral hypothalamus
12F
212
22 8
88 7
no h~stology
98
11 7
90 1
no lustology
14E
212
10 8
54 7
sub-coerulean tract
57
13 7
86 5
lateral hypothalamus
NOTE
In cases where two mtensHles appear for an ammal at a site, tile unstarred intensity Is that wluch was used during tile 6-day escape trials The starred intensity Js that which supported both escape and self-stmlulatlon behaviors
t h e a m m a l s ' a p p a r e n t d i f f i c u l t y m t r a n s f e r r i n g e s c a p e responding from dorsal bramstem to lateral hypothalamlc shmulahon, suggesting that the ammals' phenomenal exper-
lences under the mfluence of dorsal bramstem electrical s t i m u l a t i o n are q u a h t a t l v e l y d i f f e r e n t f r o m t h o s e u n d e r lateral hypothalamlc stimulahon
REFERENCES l
2
3 4
5
Beer, B and S. Sterner An analysis of the ambivalent properties of electrical brain stimulation. Paper presented at the Psychononucs Society, Chicago, llhnols, 1965. Bower, G H. and N E Miller Rewarding and p u m s h m g effects from stimulating the same place m the rat's brain J comp phystol Psyehol 51: 6 6 9 - 6 7 4 , 2958 Cooper, R. M. and L H Taylor Thalamlc reticular system and central grey sell'-shmulatlon Science 1 5 6 : 1 0 2 203, 1967 Deutsch, J A , ('. I. Howarth, G G Ball and D Deutsch Threshold dffferentmtlon o f drive and reward m tile Olds effect Nature 196: 699- 700, 2962 Farber, J., S Stelner and S. J Ellman The pons as an electrical self-stimulation site Psyehophystology 9: 105, 1972. (Abstract)
6
Margules, D L Noradrenerglc rather than serotonerglc basis ol reward m the dorsal t e g m e n t u m J comp pto,stol Psvchol 67: 32 35, 1969 7 Olds, J and P Mdner Positive r e m l o r c e m e n t produced by electrical stmlulatlon o f septal area and other regions ol the rat brain J comp phystol Psychol 4 7 : 4 1 9 429, 1954 8 OIds, J A p r e h m m a r y m a p p m g o f e l e c m c a l r e m l o r c m g e t l e c t s in the rat brain J comp phystol Psvchol 49: 281, 1956 9. Olds, J Self-stnnlatlon of tile brain Science 127: 315, 2958 IO Sterner, S., B Beer and M Schaffcr Escape from sell-produce,' rates of b r a l n s t l m u l a t l o n Scwnce 1 6 3 : 9 0 92, 1969