Pharmacology Biochemistry & Behavior, Vol. 3, pp. 1149--1151. Copyright © 1975 by ANKHO International Inc. All rights of reproduction in any form reserved. Printed in the U.S.A.
BRIEF COMMUNICATION Chlordiazepoxide and Preference for Free Food in Rats N. C. T Y E , D. J. N I C H O L A S A N D M. J. M O R G A N
The Psychological Laboratory, University o f Cambridge, Downing Street, Cambridge CB2 3EB, England (Received 25 F e b r u a r y 1975) TYE, N. C., D. J. NICHOLAS AND M. J. MORGAN. Chlordiazepoxide and preference for free food in rats. PHARMAC. BIOCHEM. BEHAV. 3(6) 1149-1151, 1975. Rats continued to lever press for food when abowl of free food was placed in the experimental chamber. Chlordiazepoxide increased the amount of free food consumed, and tended to reduce the amount of lever pressing. It is argued that the drug decreased container neophobia in the animals, rather than acting like an increase in food deprivation. Chlordiazepoxide
Food consumption
Lever pressing
T H E R E has been m u c h speculation about the increases in eating behaviour elicited by benzodiazepines [6, 15, 16]. More specifically, it is not clear w h e t h e r the increased eating reflects the reduction of anxiety, previously suppressing f o o d intake [ 11 ], or is a result of a more specific action on hunger or satiety mechanisms [9]. Wise and Dawson [19] concluded that neither explanation could account for all their experimental results. The p r o b l e m could probably be resolved by a test that dissociated the effects of hunger and reduced anxiety on eating behaviour in the rat. A possibility is lever pressing in the presence of free f o o d [7,13]. If rats are trained to lever press for pellets, they will c o n t i n u e to press to a certain e x t e n t even when a bowl of identical pellets is introduced into the apparatus. Typically, the animals begin each session by sampling the free food and then return to an e x t e n d e d b o u t o f lever pressing [ 1 3 , 1 8 [ . An increase in food deprivation raises the c o n s u m p t i o n b o t h of free and earned pellets [14] but it has a relatively greater enhancing effect upon lever pressing [14,18]. Thus, if a drug has an effect analogous to that of food deprivation, one would expect it to increase b o t h the a m o u n t of lever pressing, and the c o n s u m p t i o n of free f o o d ; and to increase the ratio of earned to free pellets. On the o t h e r hand, there is no reason why anxiety r e d u c t i o n should have such an effect, and a certain a m o u n t of evidence suggests that it might have the opposite effect. It has been suggested [10,111 that lever pressing in the presence of free food is related to container n e o p h o b i a in the rat [3]. The greater the animals' familiarity with the free food container the more they will eat from it [1 1]; also, those rats that show the greatest timidity in eating from a novel container in their h o m e cage, show the least eating of free f o o d in the operant situation. F u r t h e r evidence for the n e o p h o b i a interpreta1149
Free food
Hunger
tion is that rats reared in social isolation eat less free food than socially-reared animals [14]. Isolates are also more timid than social rats in an emergence test of exploration [12] and speed of emergence in social and isolated rats is differentially affected by chlordiazepoxide [5]. This is just one example of the well-established change in responsivity to a n u m b e r of drugs following long-term isolation in rodents [1, 2, 8, 17]. If a drug reduces timidity in rats, it might be expected to increase the c o n s u m p t i o n of food from a novel container. We therefore studied the effects of chlordiazepoxide upon lever pressing in the presence of free food, in the hope that the results might decide b e t w e e n the hunger and anxiety interpretations of drug-induced eating. METHOD
Animals Ten male Wistar rats weighing b e t w e e n 250 and 275 g, housed in pairs and kept at 85 percent free-feeding weight were used in E x p e r i m e n t 1. The animals of E x p e r i m e n t 2 were 16 male Lister h o o d e d rats (Animal Suppliers Ltd.) weighing between 250 and 350 g, and kept on an ad lib diet of laboratory chow. In b o t h e x p e r i m e n t s water was available in the h o m e cages throughout.
Apparatus The operant chambers in b o t h experiments were 4 Campden Instruments CI-410 2-1ever rat boxes with an a u t o m a t i c magazine delivering 45 mg Noyes Sucrose pellets. Rewards were delivered into a recess between the 2 levers, in front of which was a 5 cm wide transparent flap which the rat had to push open with its head to collect pellets. General illumination came from a 2.8 W houselight on the
1150
TYE, N I C H O L A S A N D M O R G A N
ceiling. The food tray was i l l u m i n a t e d w i t h a 2.8 W light w h e n a pellet was delivered, the light going o f f again w h e n the pellet h a d b e e n collected. Each c h a m b e r was e n c l o s e d in a ventilated, s o u n d - r e s i s t a n t h o u s i n g ; p r o g r a m m i n g e q u i p m e n t was located in a d i f f e r e n t r o o m . T h e sucrose pellets used as rewards (3.9 Kcal/g) are highly palatable to the l a b o r a t o r y rat, and have the following c o m p o s i t i o n : Sucrose (92.4 p e r c e n t ) , S t a r c h (4.7 p e r c e n t ) , Calcium Stearate (2.3 p e r c e n t ) , Water (0.6 p e r c e n t ) . In the first e x p e r i m e n t the free food was placed in e a r t h e n w a r e bowls (6.0 cm dia.); and in the s e c o n d e x p e r i m e n t in t o b a c c o tins (10.5 x 8.0 × 2.5 cm; tins were s u b s t i t u t e d in the s e c o n d e x p e r i m e n t to p e r m i t electrical r e c o r d i n g of c o n t a c t s , for the purpose of a n o t h e r e x p e r i m e n t ) .
10
FREE 9 8
7
6 I
5 o) v
Procedure In b o t h e x p e r i m e n t s , animals were t r a i n e d to press the left-hand lever for single-pellet rewards. Each lever press switched off the houselight, s w i t c h e d on the f o o d - t r a y light, and delivered a single pellet into the tray. F u r t h e r presses on the lever h a d n o effect until the rat p u s h e d o p e n the flap in f r o n t of the f o o d tray, at w h i c h p o i n t t h e tray light w e n t off and the h o u s e l i g h t came b a c k o n again. Session length was 20 min in E x p e r i m e n t 1 and 30 m i n in E x p e r i m e n t 2. W h e n r e s p o n d i n g h a d stabilized, the free food bowl ( E x p e r i m e n t 1) or tin ( E x p e r i m e n t 2), c o n t a i n ing 7 5 - 1 0 0 g of the reward pellets was placed against the back wall of the c h a m b e r . In E x p e r i m e n t 1, 5 o f the rats were injected i n t r a p e r i t o n e a l l y an h o u r b e f o r e testing w i t h c h l o r d i a z e p o x i d e HCL ( L i b r i u m , R o c h e ; 7.5 m g / k g in saline); the o t h e r 5 rats received c o n t r o l saline injections (1 ml/kg). T h e dosage was c h o s e n o n the basis of previous work on the effects of c h l o r d i a z e p o x i d e u p o n e m e r g e n c e in rats [ 5 ] . At the end o f the 20 m i n session the bowl of free food was weighed to d e t e r m i n e h o w m a n y pellets had b e e n c o n s u m e d . T h e p r o c e d u r e in E x p e r i m e n t 2 was t h e same e x c e p t t h a t the rats were divided into 4 groups of 4, a n d received injections of saline, 4, 8 a n d 12 m g / k g o f c h l o r d i a z e p o x i d e respectively. RESULTS
Experiment 1 The m e a n free food c o n s u m e d from the b o w l was 5.5 g in the drug g r o u p and 3.1 in the controls. This e n h a n c i n g effect of the drug was highly significant (Analysis of variance; F ( I , 9 ) = 10.5, p = 0.01). T h e drug, h o w e v e r , caused a non-significant decrease in the n u m b e r of pellets earned b y lever pressing (1.0 g in the drug g r o u p ; 1.89 g in the controls, F ( 1 , 9 ) = 1.25, p = 0.29). T h u s the relative a m o u n t of free food e a t e n was increased b y t h e drug, in m a r k e d c o n t r a s t to the effects of an increase in f o o d d e p r i v a t i o n [ 1 4 , 1 8 ] . To investigate this f u r t h e r , we carried o u t a s t u d y using n o n - d e p r i v e d rats, and several doses of the drug.
Experiment 2 The m e a n data and s t a n d a r d errors are s h o w n in Fig. 1. The drug increased c o n s u m p t i o n of free f o o d at all doses. An analysis o f variance s h o w e d t h a t t h e d i f f e r e n c e s b e t w e e n the 4 groups in free f o o d c o n s u m p t i o n were highly significant, F ( 3 , 1 2 ) = 11.2, p = 0 . 0 0 0 8 5 . As in t h e first e x p e r i m e n t , h o w e v e r , t h e effect u p o n t h e n u m b e r of e a r n e d
o o u.
I 4 I
I
I
I
I
I
I
I
I
3 2 1 ~ma*~°s*'Ja~*mme 0
, 0
t
........... "~ ........................ • ........................~ EARNED 4
8
12
CHLORDIAZEPOXIDE (mglkg)
FIG. l. Results of Experiment 2, which investigated tile effects of different dosages (abscissa) of chlordiazepoxide upon consumption of sucrose pellets (ordinate) from two different sources in the same operant chamber. Free pellets were available from a container; earned pellets were available by pressing a lever. The data show that the drug selectively enhanced consumption of the free food.
pellets was n o n - s i g n i f i c a n t l y in the reverse direction, F ( 3 , 1 2 ) = 1.276, p = 0.3. T h u s the p r o p o r t i o n of free pellets t a k e n increased w i t h each dose of the drug. GENERAL DISCUSSION
In b o t h e x p e r i m e n t s the drug increased c o n s u m p t i o n of the free food, b u t had a non-significant effect in the reverse d i r e c t i o n u p o n lever pressing. T h e reliability o f the p h e n o m e n o n is a t t e s t e d to by t h e fact t h a t the t w o e x p e r i m e n t s e m p l o y e d d i f f e r e n t strains o f animals u n d e r d i f f e r e n t c o n d i t i o n s of f o o d d e p r i v a t i o n . C o m p a r i s o n b e t w e e n the t w o saline c o n t r o l groups in the t w o experim e n t s reinforces the p o i n t t h a t d e p r i v a t i o n has a very different effect f r o m t h a t of the drug. The deprived rats in t h e first e x p e r i m e n t c o n s u m e d 3.1 g of free food and earned 1.89 g; the n o n - d e p r i v e d animals of the second e x p e r i m e n t ate 2.7 g of free food and earned only 1.1 g. If these small differences are due, at least in part, to d e p r i v a t i o n c o n d i t i o n s , it agrees w i t h previous r e p o r t s [14,18] t h a t d e p r i v a t i o n selectively e n h a n c e s lever pressing. The drug, on t h e o t h e r h a n d , selectively e n h a n c e d cons u m p t i o n of free food. This c a n n o t be reconciled with the view t h a t the drug causes an increase in hunger. The results are c o n s i s t e n t w i t h an a n x i e t y or t i m i d i t y e x p l a n a t i o n . Verification of our h y p o t h e s i s t h a t c h l o r d i a z e p o x i d e reduces n e o p h o b i a , or reluctance to eat in a novel situation,
CHLORDIAZEPOXIDE AND FREE FOOD
1151
will d e m a n d s t u d y o f t h e i n t e r a c t i o n s b e t w e e n t h e drug a n d ,other t r e a t m e n t s t h o u g h t to a f f e c t t i m i d i t y . We are ,currently investigating t h e effects of t h e drug u p o n differences b e t w e e n social a n d isolated rats in t h e free f o o d s i t u a t i o n . A n o t h e r a p p r o a c h w o u l d be to investigate effects o f the drug u p o n b e h a v i o u r t h o u g h t to be r e l a t e d to w o r k in t h e p r e s e n c e o f free food. O n e s u c h b e h a v i o u r is t r a n s p o r t o f f o o d in mazes f r o m u n f a m i l i a r t o familiar locations [4]. A recent investigation by Cohen-Salmon
( u n p u b l i s h e d Ph.D. thesis) suggests t h a t c h l o r d i a z e p o x i d e does i n d e e d r e d u c e t h e t e n d e n c y t o t r a n s p o r t in a way t h a t w o u l d be p r e d i c t e d b y o u r h y p o t h e s i s . ACKNOWLEDGEMENTS Supported by Grant 972/536/B from the Medical Research Council. N. Tye is supported by an S.R.C. scholarship. We thank Professor O. L. Zangwi/l for the facilities of the Psychological Laboratory.
REFERENCES l. 2. 3. ,l. 5. 6.
7. 8. 9.
Adler, M. W., C. Bendotti, D. Ghezzi, R. Samanin and L. Valzelli. Dependence to morphine in differentially housed rats. Psychopharmacologia 41 : 15-18, 1975. Adler, M. W., C. Manron, R. Samanin and L. Valzelli. Morphine analgesia in groups and isolated rats. Psychopharmacologia 41 : 11-14, 1975. Barnett, S. A. A Study in Behaviour: Principles of Ethology and Behavioural Physiology, Displayed Mainly in the Rat. London: Methuen, 1963, pp. 28-31. Cohen-Salmon, C. and M. Blanchetean. Transport et consommation de la nourriture dans un parcours exp6rimental chez le rat blanc. Annie psychol. 67: 377-384, 1967. Einon, D. and N. C. Tye. Chlordiazepoxide and isolation induced timidity in rats. Psychopharmacologia 44: 83-85, 1975. Jarvik, M. E. Drugs used in the treatment of psychiatric disorders. In: The Pharmacological Basis of Therapeutics (3rd Edition), edited by L. S. Goodman and A. Gilman. New York: Macmillan, 1965, pp. 159-214. Jensen, G. D. Preference for barpressing over "freeloading" as a function of number of rewarded presses. J. exp. Psychol. 65: 4 5 1 - 4 5 4 , 1963. Katz, D. M. and H. Steinberg. Long-term isolation in rat reduces morphine response. Nature 228: 4 6 9 - 4 7 1 , 1970. Margules, D. L. and L. Stein. Neuroleptics vs tranquillizers: Evidence from animals of mode and site of action. In: Neuro-Psychopharmacology, edited by H. Brill, J. O. Cole, P. Deniker, H. Hippius and P. B. Bradley. Amsterdam: Excerpta Medica, 1967.
10. Mitchell, D., K. D. Williams and J. Sutter. Container neophobia as a predictor of preference for earned food by rats. Bull. Psychon. Soc. 4: 182-184, 1974. 11. Mitchell, D., D. Winfield Scott and K. D. Williams. Container neophobia and the rat's preference for earned food. Behav. Biol. 9: 6 1 3 - 6 2 4 , 1973. 12. Morgan, M. J. Effects of post-weaning environment on learning in the rat. Anita. Behav, 21: 4 2 9 - 4 4 2 , 1973. 13. Morgan, M. J. Resistance to satiation. Anim. Behav. 22: 4 4 9 - 4 6 6 , 1974. 14. Morgan, M. J., D. F. Einon and D. Nicholas. The effects of isolation rearing on behavioural inhibition in the rat. J. exp. Psychol, in press. 15. Niki, H. Chlordiazepoxide and food intake in the rat. ,lap. psychol. Res. 7: 8 0 - 8 5 , 1965. 16. Randall, L. O., W. Schallek, G. A. Heise, E. F. Keith and R. F. Bagdon. The psychosedative properties of methaminodiazepoxide. Z pharmac, exp. Ther. 129: 163-171, 1960. 17. Sahakian, B. J., T. W. Robbins, M. J. Morgan and S. D. Iversen. The effects of psychomotor stimulants on stereotypy and locomotor activity in socially-deprived and control rats. Brain Res. 84: 195-205, 1975. 18. Tarte, R. D. and R. L. Snyder. Barpressing in the presence of free food as a function of food deprivation. Psychon. Sci. 26: 169-170, 1972. 19. Wise, R. A. and V. Dawson. Diazepam-induced eating and lever pressing for food in sated rats. J. comp. Physiol. Psychol. 86: 9 3 0 - 9 4 1 , 1974.
BRIEF COMMUNICATION Chlordiazepoxide and Preference for Free Food in Rats N. C. T Y E , D. J. N I C H O L A S A N D M. J. M O R G A N
The Psychological Laboratory, University o f Cambridge, Downing Street, Cambridge CB2 3EB, England (Received 25 F e b r u a r y 1975) TYE, N. C., D. J. NICHOLAS AND M. J. MORGAN. Chlordiazepoxide and preference for free food in rats. PHARMAC. BIOCHEM. BEHAV. 3(6) 1149-1151, 1975. Rats continued to lever press for food when abowl of free food was placed in the experimental chamber. Chlordiazepoxide increased the amount of free food consumed, and tended to reduce the amount of lever pressing. It is argued that the drug decreased container neophobia in the animals, rather than acting like an increase in food deprivation. Chlordiazepoxide
Food consumption
Lever pressing
T H E R E has been m u c h speculation about the increases in eating behaviour elicited by benzodiazepines [6, 15, 16]. More specifically, it is not clear w h e t h e r the increased eating reflects the reduction of anxiety, previously suppressing f o o d intake [ 11 ], or is a result of a more specific action on hunger or satiety mechanisms [9]. Wise and Dawson [19] concluded that neither explanation could account for all their experimental results. The p r o b l e m could probably be resolved by a test that dissociated the effects of hunger and reduced anxiety on eating behaviour in the rat. A possibility is lever pressing in the presence of free f o o d [7,13]. If rats are trained to lever press for pellets, they will c o n t i n u e to press to a certain e x t e n t even when a bowl of identical pellets is introduced into the apparatus. Typically, the animals begin each session by sampling the free food and then return to an e x t e n d e d b o u t o f lever pressing [ 1 3 , 1 8 [ . An increase in food deprivation raises the c o n s u m p t i o n b o t h of free and earned pellets [14] but it has a relatively greater enhancing effect upon lever pressing [14,18]. Thus, if a drug has an effect analogous to that of food deprivation, one would expect it to increase b o t h the a m o u n t of lever pressing, and the c o n s u m p t i o n of free f o o d ; and to increase the ratio of earned to free pellets. On the o t h e r hand, there is no reason why anxiety r e d u c t i o n should have such an effect, and a certain a m o u n t of evidence suggests that it might have the opposite effect. It has been suggested [10,111 that lever pressing in the presence of free food is related to container n e o p h o b i a in the rat [3]. The greater the animals' familiarity with the free food container the more they will eat from it [1 1]; also, those rats that show the greatest timidity in eating from a novel container in their h o m e cage, show the least eating of free f o o d in the operant situation. F u r t h e r evidence for the n e o p h o b i a interpreta1149
Free food
Hunger
tion is that rats reared in social isolation eat less free food than socially-reared animals [14]. Isolates are also more timid than social rats in an emergence test of exploration [12] and speed of emergence in social and isolated rats is differentially affected by chlordiazepoxide [5]. This is just one example of the well-established change in responsivity to a n u m b e r of drugs following long-term isolation in rodents [1, 2, 8, 17]. If a drug reduces timidity in rats, it might be expected to increase the c o n s u m p t i o n of food from a novel container. We therefore studied the effects of chlordiazepoxide upon lever pressing in the presence of free food, in the hope that the results might decide b e t w e e n the hunger and anxiety interpretations of drug-induced eating. METHOD
Animals Ten male Wistar rats weighing b e t w e e n 250 and 275 g, housed in pairs and kept at 85 percent free-feeding weight were used in E x p e r i m e n t 1. The animals of E x p e r i m e n t 2 were 16 male Lister h o o d e d rats (Animal Suppliers Ltd.) weighing between 250 and 350 g, and kept on an ad lib diet of laboratory chow. In b o t h e x p e r i m e n t s water was available in the h o m e cages throughout.
Apparatus The operant chambers in b o t h experiments were 4 Campden Instruments CI-410 2-1ever rat boxes with an a u t o m a t i c magazine delivering 45 mg Noyes Sucrose pellets. Rewards were delivered into a recess between the 2 levers, in front of which was a 5 cm wide transparent flap which the rat had to push open with its head to collect pellets. General illumination came from a 2.8 W houselight on the
1150
TYE, N I C H O L A S A N D M O R G A N
ceiling. The food tray was i l l u m i n a t e d w i t h a 2.8 W light w h e n a pellet was delivered, the light going o f f again w h e n the pellet h a d b e e n collected. Each c h a m b e r was e n c l o s e d in a ventilated, s o u n d - r e s i s t a n t h o u s i n g ; p r o g r a m m i n g e q u i p m e n t was located in a d i f f e r e n t r o o m . T h e sucrose pellets used as rewards (3.9 Kcal/g) are highly palatable to the l a b o r a t o r y rat, and have the following c o m p o s i t i o n : Sucrose (92.4 p e r c e n t ) , S t a r c h (4.7 p e r c e n t ) , Calcium Stearate (2.3 p e r c e n t ) , Water (0.6 p e r c e n t ) . In the first e x p e r i m e n t the free food was placed in e a r t h e n w a r e bowls (6.0 cm dia.); and in the s e c o n d e x p e r i m e n t in t o b a c c o tins (10.5 x 8.0 × 2.5 cm; tins were s u b s t i t u t e d in the s e c o n d e x p e r i m e n t to p e r m i t electrical r e c o r d i n g of c o n t a c t s , for the purpose of a n o t h e r e x p e r i m e n t ) .
10
FREE 9 8
7
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5 o) v
Procedure In b o t h e x p e r i m e n t s , animals were t r a i n e d to press the left-hand lever for single-pellet rewards. Each lever press switched off the houselight, s w i t c h e d on the f o o d - t r a y light, and delivered a single pellet into the tray. F u r t h e r presses on the lever h a d n o effect until the rat p u s h e d o p e n the flap in f r o n t of the f o o d tray, at w h i c h p o i n t t h e tray light w e n t off and the h o u s e l i g h t came b a c k o n again. Session length was 20 min in E x p e r i m e n t 1 and 30 m i n in E x p e r i m e n t 2. W h e n r e s p o n d i n g h a d stabilized, the free food bowl ( E x p e r i m e n t 1) or tin ( E x p e r i m e n t 2), c o n t a i n ing 7 5 - 1 0 0 g of the reward pellets was placed against the back wall of the c h a m b e r . In E x p e r i m e n t 1, 5 o f the rats were injected i n t r a p e r i t o n e a l l y an h o u r b e f o r e testing w i t h c h l o r d i a z e p o x i d e HCL ( L i b r i u m , R o c h e ; 7.5 m g / k g in saline); the o t h e r 5 rats received c o n t r o l saline injections (1 ml/kg). T h e dosage was c h o s e n o n the basis of previous work on the effects of c h l o r d i a z e p o x i d e u p o n e m e r g e n c e in rats [ 5 ] . At the end o f the 20 m i n session the bowl of free food was weighed to d e t e r m i n e h o w m a n y pellets had b e e n c o n s u m e d . T h e p r o c e d u r e in E x p e r i m e n t 2 was t h e same e x c e p t t h a t the rats were divided into 4 groups of 4, a n d received injections of saline, 4, 8 a n d 12 m g / k g o f c h l o r d i a z e p o x i d e respectively. RESULTS
Experiment 1 The m e a n free food c o n s u m e d from the b o w l was 5.5 g in the drug g r o u p and 3.1 in the controls. This e n h a n c i n g effect of the drug was highly significant (Analysis of variance; F ( I , 9 ) = 10.5, p = 0.01). T h e drug, h o w e v e r , caused a non-significant decrease in the n u m b e r of pellets earned b y lever pressing (1.0 g in the drug g r o u p ; 1.89 g in the controls, F ( 1 , 9 ) = 1.25, p = 0.29). T h u s the relative a m o u n t of free food e a t e n was increased b y t h e drug, in m a r k e d c o n t r a s t to the effects of an increase in f o o d d e p r i v a t i o n [ 1 4 , 1 8 ] . To investigate this f u r t h e r , we carried o u t a s t u d y using n o n - d e p r i v e d rats, and several doses of the drug.
Experiment 2 The m e a n data and s t a n d a r d errors are s h o w n in Fig. 1. The drug increased c o n s u m p t i o n of free f o o d at all doses. An analysis o f variance s h o w e d t h a t t h e d i f f e r e n c e s b e t w e e n the 4 groups in free f o o d c o n s u m p t i o n were highly significant, F ( 3 , 1 2 ) = 11.2, p = 0 . 0 0 0 8 5 . As in t h e first e x p e r i m e n t , h o w e v e r , t h e effect u p o n t h e n u m b e r of e a r n e d
o o u.
I 4 I
I
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3 2 1 ~ma*~°s*'Ja~*mme 0
, 0
t
........... "~ ........................ • ........................~ EARNED 4
8
12
CHLORDIAZEPOXIDE (mglkg)
FIG. l. Results of Experiment 2, which investigated tile effects of different dosages (abscissa) of chlordiazepoxide upon consumption of sucrose pellets (ordinate) from two different sources in the same operant chamber. Free pellets were available from a container; earned pellets were available by pressing a lever. The data show that the drug selectively enhanced consumption of the free food.
pellets was n o n - s i g n i f i c a n t l y in the reverse direction, F ( 3 , 1 2 ) = 1.276, p = 0.3. T h u s the p r o p o r t i o n of free pellets t a k e n increased w i t h each dose of the drug. GENERAL DISCUSSION
In b o t h e x p e r i m e n t s the drug increased c o n s u m p t i o n of the free food, b u t had a non-significant effect in the reverse d i r e c t i o n u p o n lever pressing. T h e reliability o f the p h e n o m e n o n is a t t e s t e d to by t h e fact t h a t the t w o e x p e r i m e n t s e m p l o y e d d i f f e r e n t strains o f animals u n d e r d i f f e r e n t c o n d i t i o n s of f o o d d e p r i v a t i o n . C o m p a r i s o n b e t w e e n the t w o saline c o n t r o l groups in the t w o experim e n t s reinforces the p o i n t t h a t d e p r i v a t i o n has a very different effect f r o m t h a t of the drug. The deprived rats in t h e first e x p e r i m e n t c o n s u m e d 3.1 g of free food and earned 1.89 g; the n o n - d e p r i v e d animals of the second e x p e r i m e n t ate 2.7 g of free food and earned only 1.1 g. If these small differences are due, at least in part, to d e p r i v a t i o n c o n d i t i o n s , it agrees w i t h previous r e p o r t s [14,18] t h a t d e p r i v a t i o n selectively e n h a n c e s lever pressing. The drug, on t h e o t h e r h a n d , selectively e n h a n c e d cons u m p t i o n of free food. This c a n n o t be reconciled with the view t h a t the drug causes an increase in hunger. The results are c o n s i s t e n t w i t h an a n x i e t y or t i m i d i t y e x p l a n a t i o n . Verification of our h y p o t h e s i s t h a t c h l o r d i a z e p o x i d e reduces n e o p h o b i a , or reluctance to eat in a novel situation,
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will d e m a n d s t u d y o f t h e i n t e r a c t i o n s b e t w e e n t h e drug a n d ,other t r e a t m e n t s t h o u g h t to a f f e c t t i m i d i t y . We are ,currently investigating t h e effects of t h e drug u p o n differences b e t w e e n social a n d isolated rats in t h e free f o o d s i t u a t i o n . A n o t h e r a p p r o a c h w o u l d be to investigate effects o f the drug u p o n b e h a v i o u r t h o u g h t to be r e l a t e d to w o r k in t h e p r e s e n c e o f free food. O n e s u c h b e h a v i o u r is t r a n s p o r t o f f o o d in mazes f r o m u n f a m i l i a r t o familiar locations [4]. A recent investigation by Cohen-Salmon
( u n p u b l i s h e d Ph.D. thesis) suggests t h a t c h l o r d i a z e p o x i d e does i n d e e d r e d u c e t h e t e n d e n c y t o t r a n s p o r t in a way t h a t w o u l d be p r e d i c t e d b y o u r h y p o t h e s i s . ACKNOWLEDGEMENTS Supported by Grant 972/536/B from the Medical Research Council. N. Tye is supported by an S.R.C. scholarship. We thank Professor O. L. Zangwi/l for the facilities of the Psychological Laboratory.
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