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Comparison of chlordiazepoxide and food deprivation in rats on a fixed-ratio satiation schedule
Physiology and Behavior, Vol. IO, pp. 707-710. Brain Research Publications Inc., 1973. Printed in the U.S.A.
Comparison of Chlordiazepoxide and Food Deprivation in Rats on a Fixed-ratio Satiation Schedule PAUL W. WEDEKING
Department o f Pharmacology, The Squibb Institute for Medical Research, Princeton, New Jersey 08540
(Received 27 September 1972) WEDEKING, P. W. Comparison of chlordiazepoxide and food deprivation in rats on a f'txed-ratio satiation schedule. PHYSIOL. BEHAV. 10(4) 707-710, 1973.-The effects and interactions of injected chlordiazepoxide HCI (CDP) and food deprivation in rats conditioned on a food-reinforced fixed ratio 10-satiation schedule were studied. Increasing the duration of food deprivation had no significant effect on the achievement of satiation. Decreasing the duration of deprivation produced significant decreases in responding for food pellets. Administering CDP elicited increases in responding for more reinforcements at all deprivation levels tested. The CDP effects were attributed to the disinhibition of the mechanisms regulating satiation. Chlordiazepoxide
Disinhibition
Fixed-ratio
Food deprivation
CHLORDIAZEPOXIDE HC1 (CDP) has long been k n o w n to have appetite-stimulating effects in animals [3,6]. There have been few explanations for the appetite-stimulating effect of CDP, a benzodiazepine compound widely used as a minor tranquilizer that also produces muscle relaxation and sedation [5 ]. Bainbridge [ I ] , in an assessment of the effects of psychotropic drugs on food-reinforced behavior, reported that rats injected with CDP showed increases in the number of lever responses made on a fixed-ratio (FR 4) schedule; the increase in responding was attributed to controlling fear, rather than to an increase in food-maintained behavior. Richelle, Xhenseval, Fontaine, and Thone [8] demonstrated that CDP, given to rats conditioned in either a food-reinforced fixed-interval (FI-2 rain) schedule or a differential reinforcement of low rates of responding (DRL) schedule, produced increased responding in both schedules and a disruption of DRL-timing behavior; these effects were attributed to a hypothetical interference in temporal discrimination caused by the muscle-relaxant effect of CDP. Richelle and Djahanguiri [7], investigating drug tolerance in rats, reported similar effects of CDP in rats on an FI-2 schedule. In 1967, Margules and Stein [4] proposed a theory of disinhibition to explain the effects that tranquilizers (including CDP) have on suppressed behavior. They suggested that tranquilizers could produce "stimulating" effects by blocking the normal function of mechanisms that suppress responding. In rats conditioned on a multiple FR 25, 10-sec time out
Motivation
Satiation
(TO) schedule [10] or a multiple two-lever FR 25 discrimination, 15-sec TO schedule [ l 1 ], administration of CDP produced both increased response rates during the conditioned stimulus (CS) and an increase number of TO responses. These results were attributed primarily to the disinhibitory effect of CDP and secondarily to its appetitestimulating effect. The above studies, however, did not examine the effects of satiation or deprivation on the performance of the rats in the schedules studied. The present report describes the effects of food deprivation, alone and jointly with the administration of CDP, on the petrformance of rats conditioned on an FR 10-satiation schedule with food reinforcement. METHOD
Procedure and Animals The FR-satiation schedule was a conventional FR 10 schedule with the rat's performance determining the total number of food pellets obtained during the session. The procedure was to place a rat in an operant chamber, extinguish the house light, and turn on a white light (CS) mounted 5 cm above the lever. The CS indicated that every tenth lever press would be reinforced with a 45-mg Noyes food pellet. The end of the session was determined by the rat's failure to work for a reinforcement during a 5-min period (exclusive of the first reinforcement), and was indicated to the rat by turning the CS off and the house light on. When the session terminated, it was assumed that the rat was satiated. 707
708
WEDEK1NG
Two Lehigh Valley Electronics operant chambers (No. 1 4 3 - 2 1 ) were utilized, each isolated in a ventilated, lightand sound-attenuated enclosure. The FR-satiation schedule was controlled with conventional electromechanical equipment, and the following behavioral indices recorded: (1) number of responses; (2) number of reinforcements obtained during the session; (3) latency to obtain the first reinforcement; and, (4) length of time from the first reinforcement to the termination of the session. A cumulative record was made for each session. Drinking behavior was not counted, but was visualized on the cumulative record via drinkometer circuitry ( G r a s o n - S a d l e r No. E4690A-1). Eight experimentally naive, male Long-Evans rats, approximately 200 days old at the start of experimentation, were used in the experiments. The rats were allotted to two equal-sized groups (one group for each chamber) and were housed individually. The rats performed Mondays through Fridays and reached asymptotic performance levels within 3 weeks. On Saturday and Sunday, each rat was given food pellets in its home cage equal to its mean daily consumption during the Monday through Friday sessions. (No other food was given the rats in their home cages). Water was available ad lib at all times.
Experirnents Prior to studying the effects of CDP and deprivation, preliminary experiments with the FR-satiation schedule determined that there were no significant differences in the behavioral indices studied when the criterion for session termination was 5, I0, or 20 min without reinforcement. After asymptotic performance had been achieved by the rats on the FR-10 satiation schedule, the following determinations were made: (1) the effects o f CDP, 2.5 and 5.0 mg/kg, IP on the standard 22-hr deprivation (control tests with saline were included); (2) the effects o f 2- and 46-hr deprivations; and, (3) the effects of CDP, 5.0 mg/kg, IP, on 2- and 46-hr deprivations. The two dose levels of CDP used in Experiment 1 were selected from previous CDP reports [ 1 0 , I 1 ] and were known to produce significant increases in conditioned food-reinforced behavior without eliciting ataxia or other debilitating effects. The 5 mg CDP/kg dose was selected for testing in Experiment 3 since it produced the greatest effect in Experiment I. Saline or CDP was injected intraperitoneally 10 min before the test session; CDP was administered as a solution in isotonic saline. Each rat served as its own control. The results of each session recorded served as control values for the next session. For assessing the effects of injected CDP and deprivation of food, the means for control and test values are reported and, where appropriate, standard percentages of controls (E/C x 100) are presented. Statistical significance was determined via t-tests comparing control and test data. RESULTS AND DISCUSSION The FR-satiation schedule produced conditioned behavior in rats similar to that found by Sidman and Stebbins [9] in their study of FR behavior for long periods of time ( 6 0 - 1 5 0 hr). but the calculated response rates in the present study were approximately one-half as fast. The
methods of calculating response rates differed. In their study, Sidman and Stebbins deducted the resting times and postreinforcement pauses in the F R schedules from the duration of the session before calculating the response rates, but in the present study, the times for post-reinforcement pauses (and drinking periods) were not deducted from the duration of the session. In all the studies of CDP cited, an increase in foodmaintained behavior has been reported. It appeared likely, therefore, that depriving conditioned rats of food could produce results resembling those obtained after the administration of CDP. At the beginning of this study, it was assumed that the motivation for food (appetite-stimulation) and the amount of food consumed (satiation) was proportional to the duration of deprivation. The effects of CDP administration and of food deprivation on the total number of reinforcements obtained by the rats are presented in Table 1. Increasing the duration of deprivation from 2 2 - 4 6 hr did not affect the working for food pellets as expected. The number of reinforcements obtained and consumed decreased slightly (85% of control) rather than increased, possibly as a result of inanition or stomach shrinkage [4]. Decreasing the duration of deprivation from 2 2 - 2 hr significantly decreased the number of food pellets obtained and consumed, but the amount consumed by the rats, presumably satiated only 2 hr earlier, was remarkable (55% of control). It appeared that a 2-hr interval permitted partial emptying of the stomach, thus allowing the rats to ingest more.food [ 9 ]. In Experiment 1, administering CDP produced increases in the number of reinforcements obtained and consumed at both 2.5 mg CDP/kg (116% of controlI and 5.0 mg CDP/kg (152% of control); these results resemble data from previous nonoperant food-consumption studies [ 6 ] . Muscle-relaxant effects [8] were not evident (no ataxia or other debilitation) in either CDP-treated or fooddeprived rats. It is doubtful that the fear controlling effect of CDP [1] could serve to explain the results since the FR-satiation schedule did not a p p e a r to elicit fear in the rats. Depriving the rats of food for 46 hr. a procedure commonly used to study motivation, did not increase satiation levels; i.e., an increased duration of deprivation did not make the rats work longer for more food. However, CDP administration seemed to disrupt satiation as indicated by the increases in reinforcements obtained and consumed. The disruptions were attributed to the disinhibitory effect of CDP [4,11 ]. Comparing the effects of deprivation and CDP to the deprivation effects without CDP, it seemed that as the deprivation duration decreased from 46 to 22 to 2 hr, the disinhibitory effect of CDP increased significantly. However, when the differences between the effects of deprivation alone and jointly with CDP were compared, it appeared that CDP produced similar increases in the number of reinforcements obtained irregardless of the duration of deprivation. These observations suggested that CDP was only affecting one or some of the mechanisms that influence satiation and other influences controlling satiation apparently antagonized or overpowered the disinhibitory effect of CDP. As shown in Table 1, administering CDP, varying the duration of food-drprivation, or both had no significant effect on the response rates. There are no simple explanations for the findings. Previous studies of the effects of CDP
EFFECTS OF CDP AND DEPRIVATION ON F R - S A T I A T I O N
709
TABLE 1 EFFECTS AND INTERACTIONS OF CHLORDIAZEPOXIDE AND DEPRIVATION ON VARIOUS INDICES IN RATS ON AN FR IO-SATIATION SCHEDULE
Treatment
Saline (and 22-hr Deprivation)
N
Mean Latency to First Reinforcement (Min)
MeanTotal Reinforcements Per Session
MeanResponses/Min
Control
Control
Treatment
Control
Treatment
Treatment
20
0.65
0.61
288.8
275.5
42.8
41.3
CDP - 2.5 mg/kg (and 22-hr Deprivation)
8
0.67
0.39 (p<0.10)
298.8
346.9
41.0
40.9
CDP - 5.0 mg/kg land 22-hr Deprivation)
8
0.60
0.31 (p<0.10)
272.2
414.1 (p<0.05)
41.9
40.4
2-hr Deprivation
8
0.59
5.61 (p<0.05)
283.4
157.1 (p
36.5
39.5
46-hr Deprivation
22
0.61
0.39 (p
256.9
218.5
39.0
34.5
CDP- 5.0 mg/kg (and 2-hr Deprivation)
10
1.03
4.13 (p<0.05)
267.9
276.7
49.2
41.8
13
0.59
0.44
257.1
301.0
46.2
36.5
CDP - 5.0 mg/kg (and 46-hr Deprivation)
on food-reinforced behavior emphasized that CDP produces increased response rates in the food-reinforced components of the schedules. It was possible that the rats in the present study might have performed faster at the beginning of each session and more slowly towards its end, but an examination of the cumulative records did not support this explanation. Another explanation is that the behavior in the FR-satiation schedule was so completely controlled by the schedule itself that the responding behavior was resistant to modification by the relatively low doses of CDP or by the various degrees of deprivation tested [ 2 ] ; i.e., the rats were conditioned to work at constant response rates and injecting CDP, depriving of food, or both had no significant effect on the rate of responding. Changes in the latency to first reinforcement (Table 1) suggested possible changes in the motivation for food. Rats deprived of food for 2 hr took significantly longer (compared to their control latencies) to work for their first reinforcement indicating a possible decrease in motivation for food. Conversely, rats food-deprived for 46 hr took significantly less time to work for their first reinforcement (compared to controls) suggesting an increased motivation for food. In Experiment I, similar to the data for rats
deprived of food for 46 hr, rats administered 2.5 mg CDP/kg or 5.0 mg CDP/kg took significantly less time to earn their first reinforcement again suggesting an increased motivation for food. The results of these experiments demonstrated that, in food-reinforced conditioned behavior, the increased responding for food reinforcement produced in rats by administration of CDP did not mimic completely the effects elicited by food-deprivation. Although increasing the duration of deprivation or administering CDP both appeared to increase motivation for food reinforcement, increasing the duration of deprivation apparently had no effect on achievement of satiation; however, CDP administration disrupted satiation resulting in substantial increases in the number of reinforcements obtained and consumed. These results support previous suggestions that CDP disinhibits or disrupts the mechanisms regulating satiation. ACKNOWLEDGEMENTS The author would like to thank Drs. R. G. Babington, B. Beer, and Z. P. Horovitz for their suggestions and criticism during the preparation of this report. The author is particularly indebted to Dr. D. Frost for critical editing of the manuscript.
REFERENCES 1. Brainbridge, J. G. The effect of psychotropic drugs on food reinforced behavior and on food consumption. Psychopharmacologia (Berl.) 12: 204-213, 1968. 2. Dews, P. B. Modification by drugs of performance on simple schedules of positive reinforcement. Ann. N. Y. Acad. Sci. 65: 268-281. 1956.
3. Jarvik, M. E. Drugs used in the treatment of psychiatric disorders. In: Tile Pharmacological Basis o f Therapeun'cs (3rd ed.), edited by L. S. Goodman and A. Gilman. New York: MacMillan, 1965, pp. 159-214.
710 4. Margules, D. L. and L. Stein. Neuroleptics vs. tranquilizers: Evidence from animal behavior studies of mode and site of action. In: Neuropsychopharmacology. edited by H. Brill. New York: Medica Foundation, 1967, pp. 108-120. 5. Randall, L. O. and W. SchaUek. Pharmacological activity of certain benzodiazepones. In: Psychopharmacology: A Review of Progress 1957-1967, edited by D. H. Efron. Washington, D. C.: Public Health Service Pub. No. 1836, 1968, pp. 153-184. 6. Randall, L. O., W. Schallek, G. A. Heise, E. F. Keith, and R. E. Bagdon. The psychosedative properties of methaminodiazepoxide. J. Pharmac. exp. Ther. 129: 1 6 3 - 1 7 1 , 1960. 7. RicheUe, M. and B. Djahanguiri. Effet d'un traitement prolong6 au chlordiazepoxide sur un conditionnement temporel chez le rat. Psychopharmacologia (Bed.) 5 : 106-114, 1964.
WEDEKING 8. Richelle, M.,,B. Xhenseval, D. Fontairte, and L. Thone. Action of chlordiazepoxide on two types of temporal conditioning in rats. Int. J. Neuropharmac. 1 : 3 8 1 - 3 9 1 , 1962. 9. Sidman, M, and W. C. Stebbins. Satiation effects under fixed ratio schedules of reinforcement. J. comp. physioL Psychol. 47: 114-116, 1954. 10. Wedeking, P. W. Stimulating effects of chloridazepoxide in rats on a food reinforced FR schedule. Psychon. Sci. 12: 3 1 - 3 2 , 1968. 11. Wedeking, P. W, Disinhibition effect of chlordiazepoxide. Psychon. Sci. 15: 2 3 2 - 2 3 3 , 1969.
Comparison of Chlordiazepoxide and Food Deprivation in Rats on a Fixed-ratio Satiation Schedule PAUL W. WEDEKING
Department o f Pharmacology, The Squibb Institute for Medical Research, Princeton, New Jersey 08540
(Received 27 September 1972) WEDEKING, P. W. Comparison of chlordiazepoxide and food deprivation in rats on a f'txed-ratio satiation schedule. PHYSIOL. BEHAV. 10(4) 707-710, 1973.-The effects and interactions of injected chlordiazepoxide HCI (CDP) and food deprivation in rats conditioned on a food-reinforced fixed ratio 10-satiation schedule were studied. Increasing the duration of food deprivation had no significant effect on the achievement of satiation. Decreasing the duration of deprivation produced significant decreases in responding for food pellets. Administering CDP elicited increases in responding for more reinforcements at all deprivation levels tested. The CDP effects were attributed to the disinhibition of the mechanisms regulating satiation. Chlordiazepoxide
Disinhibition
Fixed-ratio
Food deprivation
CHLORDIAZEPOXIDE HC1 (CDP) has long been k n o w n to have appetite-stimulating effects in animals [3,6]. There have been few explanations for the appetite-stimulating effect of CDP, a benzodiazepine compound widely used as a minor tranquilizer that also produces muscle relaxation and sedation [5 ]. Bainbridge [ I ] , in an assessment of the effects of psychotropic drugs on food-reinforced behavior, reported that rats injected with CDP showed increases in the number of lever responses made on a fixed-ratio (FR 4) schedule; the increase in responding was attributed to controlling fear, rather than to an increase in food-maintained behavior. Richelle, Xhenseval, Fontaine, and Thone [8] demonstrated that CDP, given to rats conditioned in either a food-reinforced fixed-interval (FI-2 rain) schedule or a differential reinforcement of low rates of responding (DRL) schedule, produced increased responding in both schedules and a disruption of DRL-timing behavior; these effects were attributed to a hypothetical interference in temporal discrimination caused by the muscle-relaxant effect of CDP. Richelle and Djahanguiri [7], investigating drug tolerance in rats, reported similar effects of CDP in rats on an FI-2 schedule. In 1967, Margules and Stein [4] proposed a theory of disinhibition to explain the effects that tranquilizers (including CDP) have on suppressed behavior. They suggested that tranquilizers could produce "stimulating" effects by blocking the normal function of mechanisms that suppress responding. In rats conditioned on a multiple FR 25, 10-sec time out
Motivation
Satiation
(TO) schedule [10] or a multiple two-lever FR 25 discrimination, 15-sec TO schedule [ l 1 ], administration of CDP produced both increased response rates during the conditioned stimulus (CS) and an increase number of TO responses. These results were attributed primarily to the disinhibitory effect of CDP and secondarily to its appetitestimulating effect. The above studies, however, did not examine the effects of satiation or deprivation on the performance of the rats in the schedules studied. The present report describes the effects of food deprivation, alone and jointly with the administration of CDP, on the petrformance of rats conditioned on an FR 10-satiation schedule with food reinforcement. METHOD
Procedure and Animals The FR-satiation schedule was a conventional FR 10 schedule with the rat's performance determining the total number of food pellets obtained during the session. The procedure was to place a rat in an operant chamber, extinguish the house light, and turn on a white light (CS) mounted 5 cm above the lever. The CS indicated that every tenth lever press would be reinforced with a 45-mg Noyes food pellet. The end of the session was determined by the rat's failure to work for a reinforcement during a 5-min period (exclusive of the first reinforcement), and was indicated to the rat by turning the CS off and the house light on. When the session terminated, it was assumed that the rat was satiated. 707
708
WEDEK1NG
Two Lehigh Valley Electronics operant chambers (No. 1 4 3 - 2 1 ) were utilized, each isolated in a ventilated, lightand sound-attenuated enclosure. The FR-satiation schedule was controlled with conventional electromechanical equipment, and the following behavioral indices recorded: (1) number of responses; (2) number of reinforcements obtained during the session; (3) latency to obtain the first reinforcement; and, (4) length of time from the first reinforcement to the termination of the session. A cumulative record was made for each session. Drinking behavior was not counted, but was visualized on the cumulative record via drinkometer circuitry ( G r a s o n - S a d l e r No. E4690A-1). Eight experimentally naive, male Long-Evans rats, approximately 200 days old at the start of experimentation, were used in the experiments. The rats were allotted to two equal-sized groups (one group for each chamber) and were housed individually. The rats performed Mondays through Fridays and reached asymptotic performance levels within 3 weeks. On Saturday and Sunday, each rat was given food pellets in its home cage equal to its mean daily consumption during the Monday through Friday sessions. (No other food was given the rats in their home cages). Water was available ad lib at all times.
Experirnents Prior to studying the effects of CDP and deprivation, preliminary experiments with the FR-satiation schedule determined that there were no significant differences in the behavioral indices studied when the criterion for session termination was 5, I0, or 20 min without reinforcement. After asymptotic performance had been achieved by the rats on the FR-10 satiation schedule, the following determinations were made: (1) the effects o f CDP, 2.5 and 5.0 mg/kg, IP on the standard 22-hr deprivation (control tests with saline were included); (2) the effects o f 2- and 46-hr deprivations; and, (3) the effects of CDP, 5.0 mg/kg, IP, on 2- and 46-hr deprivations. The two dose levels of CDP used in Experiment 1 were selected from previous CDP reports [ 1 0 , I 1 ] and were known to produce significant increases in conditioned food-reinforced behavior without eliciting ataxia or other debilitating effects. The 5 mg CDP/kg dose was selected for testing in Experiment 3 since it produced the greatest effect in Experiment I. Saline or CDP was injected intraperitoneally 10 min before the test session; CDP was administered as a solution in isotonic saline. Each rat served as its own control. The results of each session recorded served as control values for the next session. For assessing the effects of injected CDP and deprivation of food, the means for control and test values are reported and, where appropriate, standard percentages of controls (E/C x 100) are presented. Statistical significance was determined via t-tests comparing control and test data. RESULTS AND DISCUSSION The FR-satiation schedule produced conditioned behavior in rats similar to that found by Sidman and Stebbins [9] in their study of FR behavior for long periods of time ( 6 0 - 1 5 0 hr). but the calculated response rates in the present study were approximately one-half as fast. The
methods of calculating response rates differed. In their study, Sidman and Stebbins deducted the resting times and postreinforcement pauses in the F R schedules from the duration of the session before calculating the response rates, but in the present study, the times for post-reinforcement pauses (and drinking periods) were not deducted from the duration of the session. In all the studies of CDP cited, an increase in foodmaintained behavior has been reported. It appeared likely, therefore, that depriving conditioned rats of food could produce results resembling those obtained after the administration of CDP. At the beginning of this study, it was assumed that the motivation for food (appetite-stimulation) and the amount of food consumed (satiation) was proportional to the duration of deprivation. The effects of CDP administration and of food deprivation on the total number of reinforcements obtained by the rats are presented in Table 1. Increasing the duration of deprivation from 2 2 - 4 6 hr did not affect the working for food pellets as expected. The number of reinforcements obtained and consumed decreased slightly (85% of control) rather than increased, possibly as a result of inanition or stomach shrinkage [4]. Decreasing the duration of deprivation from 2 2 - 2 hr significantly decreased the number of food pellets obtained and consumed, but the amount consumed by the rats, presumably satiated only 2 hr earlier, was remarkable (55% of control). It appeared that a 2-hr interval permitted partial emptying of the stomach, thus allowing the rats to ingest more.food [ 9 ]. In Experiment 1, administering CDP produced increases in the number of reinforcements obtained and consumed at both 2.5 mg CDP/kg (116% of controlI and 5.0 mg CDP/kg (152% of control); these results resemble data from previous nonoperant food-consumption studies [ 6 ] . Muscle-relaxant effects [8] were not evident (no ataxia or other debilitation) in either CDP-treated or fooddeprived rats. It is doubtful that the fear controlling effect of CDP [1] could serve to explain the results since the FR-satiation schedule did not a p p e a r to elicit fear in the rats. Depriving the rats of food for 46 hr. a procedure commonly used to study motivation, did not increase satiation levels; i.e., an increased duration of deprivation did not make the rats work longer for more food. However, CDP administration seemed to disrupt satiation as indicated by the increases in reinforcements obtained and consumed. The disruptions were attributed to the disinhibitory effect of CDP [4,11 ]. Comparing the effects of deprivation and CDP to the deprivation effects without CDP, it seemed that as the deprivation duration decreased from 46 to 22 to 2 hr, the disinhibitory effect of CDP increased significantly. However, when the differences between the effects of deprivation alone and jointly with CDP were compared, it appeared that CDP produced similar increases in the number of reinforcements obtained irregardless of the duration of deprivation. These observations suggested that CDP was only affecting one or some of the mechanisms that influence satiation and other influences controlling satiation apparently antagonized or overpowered the disinhibitory effect of CDP. As shown in Table 1, administering CDP, varying the duration of food-drprivation, or both had no significant effect on the response rates. There are no simple explanations for the findings. Previous studies of the effects of CDP
EFFECTS OF CDP AND DEPRIVATION ON F R - S A T I A T I O N
709
TABLE 1 EFFECTS AND INTERACTIONS OF CHLORDIAZEPOXIDE AND DEPRIVATION ON VARIOUS INDICES IN RATS ON AN FR IO-SATIATION SCHEDULE
Treatment
Saline (and 22-hr Deprivation)
N
Mean Latency to First Reinforcement (Min)
MeanTotal Reinforcements Per Session
MeanResponses/Min
Control
Control
Treatment
Control
Treatment
Treatment
20
0.65
0.61
288.8
275.5
42.8
41.3
CDP - 2.5 mg/kg (and 22-hr Deprivation)
8
0.67
0.39 (p<0.10)
298.8
346.9
41.0
40.9
CDP - 5.0 mg/kg land 22-hr Deprivation)
8
0.60
0.31 (p<0.10)
272.2
414.1 (p<0.05)
41.9
40.4
2-hr Deprivation
8
0.59
5.61 (p<0.05)
283.4
157.1 (p
36.5
39.5
46-hr Deprivation
22
0.61
0.39 (p
256.9
218.5
39.0
34.5
CDP- 5.0 mg/kg (and 2-hr Deprivation)
10
1.03
4.13 (p<0.05)
267.9
276.7
49.2
41.8
13
0.59
0.44
257.1
301.0
46.2
36.5
CDP - 5.0 mg/kg (and 46-hr Deprivation)
on food-reinforced behavior emphasized that CDP produces increased response rates in the food-reinforced components of the schedules. It was possible that the rats in the present study might have performed faster at the beginning of each session and more slowly towards its end, but an examination of the cumulative records did not support this explanation. Another explanation is that the behavior in the FR-satiation schedule was so completely controlled by the schedule itself that the responding behavior was resistant to modification by the relatively low doses of CDP or by the various degrees of deprivation tested [ 2 ] ; i.e., the rats were conditioned to work at constant response rates and injecting CDP, depriving of food, or both had no significant effect on the rate of responding. Changes in the latency to first reinforcement (Table 1) suggested possible changes in the motivation for food. Rats deprived of food for 2 hr took significantly longer (compared to their control latencies) to work for their first reinforcement indicating a possible decrease in motivation for food. Conversely, rats food-deprived for 46 hr took significantly less time to work for their first reinforcement (compared to controls) suggesting an increased motivation for food. In Experiment I, similar to the data for rats
deprived of food for 46 hr, rats administered 2.5 mg CDP/kg or 5.0 mg CDP/kg took significantly less time to earn their first reinforcement again suggesting an increased motivation for food. The results of these experiments demonstrated that, in food-reinforced conditioned behavior, the increased responding for food reinforcement produced in rats by administration of CDP did not mimic completely the effects elicited by food-deprivation. Although increasing the duration of deprivation or administering CDP both appeared to increase motivation for food reinforcement, increasing the duration of deprivation apparently had no effect on achievement of satiation; however, CDP administration disrupted satiation resulting in substantial increases in the number of reinforcements obtained and consumed. These results support previous suggestions that CDP disinhibits or disrupts the mechanisms regulating satiation. ACKNOWLEDGEMENTS The author would like to thank Drs. R. G. Babington, B. Beer, and Z. P. Horovitz for their suggestions and criticism during the preparation of this report. The author is particularly indebted to Dr. D. Frost for critical editing of the manuscript.
REFERENCES 1. Brainbridge, J. G. The effect of psychotropic drugs on food reinforced behavior and on food consumption. Psychopharmacologia (Berl.) 12: 204-213, 1968. 2. Dews, P. B. Modification by drugs of performance on simple schedules of positive reinforcement. Ann. N. Y. Acad. Sci. 65: 268-281. 1956.
3. Jarvik, M. E. Drugs used in the treatment of psychiatric disorders. In: Tile Pharmacological Basis o f Therapeun'cs (3rd ed.), edited by L. S. Goodman and A. Gilman. New York: MacMillan, 1965, pp. 159-214.
710 4. Margules, D. L. and L. Stein. Neuroleptics vs. tranquilizers: Evidence from animal behavior studies of mode and site of action. In: Neuropsychopharmacology. edited by H. Brill. New York: Medica Foundation, 1967, pp. 108-120. 5. Randall, L. O. and W. SchaUek. Pharmacological activity of certain benzodiazepones. In: Psychopharmacology: A Review of Progress 1957-1967, edited by D. H. Efron. Washington, D. C.: Public Health Service Pub. No. 1836, 1968, pp. 153-184. 6. Randall, L. O., W. Schallek, G. A. Heise, E. F. Keith, and R. E. Bagdon. The psychosedative properties of methaminodiazepoxide. J. Pharmac. exp. Ther. 129: 1 6 3 - 1 7 1 , 1960. 7. RicheUe, M. and B. Djahanguiri. Effet d'un traitement prolong6 au chlordiazepoxide sur un conditionnement temporel chez le rat. Psychopharmacologia (Bed.) 5 : 106-114, 1964.
WEDEKING 8. Richelle, M.,,B. Xhenseval, D. Fontairte, and L. Thone. Action of chlordiazepoxide on two types of temporal conditioning in rats. Int. J. Neuropharmac. 1 : 3 8 1 - 3 9 1 , 1962. 9. Sidman, M, and W. C. Stebbins. Satiation effects under fixed ratio schedules of reinforcement. J. comp. physioL Psychol. 47: 114-116, 1954. 10. Wedeking, P. W. Stimulating effects of chloridazepoxide in rats on a food reinforced FR schedule. Psychon. Sci. 12: 3 1 - 3 2 , 1968. 11. Wedeking, P. W, Disinhibition effect of chlordiazepoxide. Psychon. Sci. 15: 2 3 2 - 2 3 3 , 1969.