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Effect of nicotine on response to frustrative non-reward in the rat
European Journal o f Pharmacology 29 ( 1974 ) 312 --315 © North-Ftolland Publishing Company
Short communication EFFECT OF NICOTINE ON RESPONSE THE RAT
TO FRUSTRATIVE
NON-REWARD
IN
Martin D. SCHECHTER* Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia Received 27 August 1974, accepted 4 October 1974
M.D. SCHECttTER, Effect of nicotine on response to frustrative non-reward in the rat, European J. Pharmacol. 29 (1974) 312-315. Rats were subjected to frustrative non-reward in the Amsel double runway after administration of nicotine and saline. Results revealed that nicotine decreases the magnitude of the frustrative effect when compared to saline (p < 0.01). This finding is interpreted, in light of other studies reporting a decline in aggression after nicotine administration.
Nicotine
Aggression
Frustration
I. Introduction It is well established that, following a history of reinforcement on a well learned response, the onset of extinction produces an abrupt increase in the vigor of responding (Miller and Stevenson, 1936; Crespi, 1944). This increased vigor is thought to reflect a state o f aggression since it increases the tendency of the animal subject to attack other animals or objects in the experimental space (Azrin et al., 1966; Thompson and Bloom, 1966). Amsel and Roussel (1952) observed that when a running response in rats had been maximally elicited under hunger motivation, the addition o f non-reward resulted in the establishment of a new and higher maximum running speed. By comparing response rates (running speeds) immediately before and after the occurrence of non-reward, it was possible to quantify the behavioral effects (aggressiveness) of the extinction (frustration) operation. In the light of recent investigations reporting the ability o f nicotine to decrease various types of aggres* Supported by a grant from the American Medical Association Education and Research Foundation. Present address: Department of Pharmacology, Eastern Virginia Medical School, Norfolk, Virginia 23507, U.S.A.
Runway
Rat
siveness in rats (Silverman, 1970) squirrel monkeys (Emley et al., 1971), ants (Kostowski, 1968) and man (Schechter and Rand, 1974), the present study sought to investigate if nicotine would affect increased aggression as defined as the after-effect o f non-reinforcement in a previously reinforced response.
2. Materials and methods 2.1. Measurement o f running speeds 10 experimentally naive, female hooded rats, 120 days old at the beginning o f experimentation, were housed individually with free access to food and water until the fifth day of experimental adaptation. The apparatus consisted of a straight 247.3 cm plastic alley divided in the following order: a 30.5 cm long start box, 91.4 cm long runway, 30.5 cm goal box, a second 91.4 cm runway and second goal box. The inside dimensions o f the alley were 20.3 cm wide and 16.5 cm high. All areas were the same color and fitted with hinged transparent tops to facilitate viewing and removal. Retrace doors were used at the front of each goal box to insure that once the rat had en-
M.D. Schechter, Nicotine and rat's response to frustrative non-reward
tered the box it could not retreat. Manually operated guillotine doors served as exits from the start box and goal boxes. A photoelectric cell, mounted 4.3 cm from the floor, was located 13.9 cm from the guillotine door of the first goal box, in the first section of the second runway. When this light beam was broken, by the passing of the rat, a Yunker Electronics msec timer was activated. A second photoelectric cell was located 61 cm farther along the second runway at a point 7.6 cm from the retrace door of the second goal box, and when this light was interrupted the msec timer was stopped. Thus, the time to run 61 cm of the 91.4 cm long second runway could be measured in msec. 2.2. Procedure
Before formal training began, the rats underwent 10 days of adaptation to the experimental environment. The first 5 days were spent in adapting the rats to handling and free exploration of the apparatus. Each rat was handled for I0 min each day, and allowed 5 min in the apparatus with the partitioning doors opened and food placed in both goal boxes. During the next 5 days, the rats received only enough food in their home cages to maintain them at 80% body weight and each rat was trained io push open the retrace doors to gain admission to each goal box to obtain food. During training, each rat was injected s.c. with a constant volume of 1 ml/kg of saline (0.9% NaCI solution) and 15 min later, it was placed into the start box. The trial began with the opening of the guillotine door when the rat had oriented forward. The rat traversed the first runway, entered the first goal box and ate the food provided. After 15 sec access to the food, the guillotine door of the first goal box was raised and the rat negotiated the second runway and entered the second goal box to obtain the food provided. During this phase of the study, the following conditions were standard: 2 trials per day, one at 8 am and the second at 3 pm; saline administered 15 rain prior to the start of all trials; reinforcement, consisting of 4 0.05 g specially compounded food pellets, provided in both goal boxes; 15 sec retention time in the first goal box and running speeds in the second runway recorded. By the seventieth trial with saline administration
313
and food provided in both goal boxes, the running speeds for all rats had stabilized. The procedure was altered after trial 89 to consist of one of the following 4 treatments: (1) Saline reinforcement (Sr) - saline administration with food provided in both goal boxes; (2) Saline frustration (SO - saline administration with no food in the first goal box; (3) Nicotine reinforcement (Nr) - nicotine administration with food provided in both goal boxes: and (4) Nicotine frustration (N O - nicotine administration with no food provided in the first goal box. All injections were s.c. at a constant volume of I ml/kg body weight and each trial began 15 min post-injection. The administration sequence of the 4 treatments was randomized with all rats receiving 2 treatments per day. Retention time in the first goal box was 15 sec for both reinforcement and non-reinforcement trials and food always provided in the second goal box. The dosages of nicotine used, in 2 blocks of experiments, were 0.4 and 0.8 mg/kg with 0.9% saline used as vehicle and doses calculated as base. The data, in terms of mean running speeds for each rat in the second runway, were analyzed by analysis of variance. When the level of significance of the withinsubject statistic exceeded p < 0 . 0 1 , the NewmanKeul's test on differences between pairs of means (Winer, 1962)was applied to evaluate levels of significance between specific treatments, i.e.,Nr vs. St', Sr vs. Sf, Nf vs. Sf, Nr vs. St, Nr vs. Nf, Nf vs. Sr, at each dose level of nicotine used.
3. Results Frustration is measured in the double runway as increased running speed in runway 2 on those trials in which reinforcement is omitted from goal box 1. Table 1 presents mean running speeds under the various experimental conditions. Analysis of the data, by evaluating the mean running speed of each of 10 rats in each condition, revealed that a statistically significant difference exists between the 4 conditions after 0.4 mg/kg nicotine (F = 62.85; df = 3/27;p < 0.01); and after 0.8 mg/kg nicotine (F = 64.93; df = 3/27; p <0.01). Evaluation of the data by the Newman-Keul's test on differences between pairs of means for each treatment shows that there was a significant difference
314
M.D. Schechter, Nicotine and rat's response to frustrative non-reward
Table 1 Mean running times in runway 2 for four treatments. Treatment: nicotine dose (mg/kg)
Nr
Sr
Nf
Sf
No. of trials for each treatment
F-value2
df
0.4 0.8
882.71 892.3
881.2 891.8
873.4 879.4
866.8 860.4
8 4
62.85 64.93
3/27 3/27
l Each value is the mean running time in msec of 10 rats in the number of trials for each treatment. 2F-value is the within-subject statistic derived by analysis of variance; in both eases p < 0.01.
( p < 0 . 0 1 ) between all treatments except those between Sr and Nr. Thus, the relationship of running speeds, at both doses of nicotine, for the treatments given is Nr = Sr < Nf < Sf. Nicotine administration had no effect on running speeds when compared to saline in the reinforcement trials, whereas, frustrative non-reward trials produced significantly faster running speeds when compared to reinforcement trials, with the administration of both saline and nicotine. The administration of both doses of nicotine produced significantly slower mean running speeds under frustrative non-reward than did the administration of saline.
4. Discussion The results of this study confirm the observations reported by Amsel and Roussel (1952) to prove the 'frustrative non-reward' theory. The mean running speed of the 10 rats before nicotine administration and frustrative trials was 881.5 msec, and the mean running speed for Sr trials during the first trial block with 0.4 mg/kg nicotine remained at 881.2 msec. The initiation of frustration trials after saline administration (SO produced an increase in mean running speed to 866.8 msec. Thus, the maximally elicited running speed after saline and reinforcement was shown to increase to a new and higher maximum running speed by the addition of frustration to the motivational complex. The administration of nicotine, at doses of 0.4 and 0.8 mg/kg was shown to be unable to block the effect of frustrative non-reward on running speed, i.e., the mean running speeds with nicotine and reinforcement were always significantly more than with nicotine and
frustration (Nr < Nf). Nicotine had no effect on mean running speeds during reinforcement trials when compared with saline (Nr = Sr). However, running speeds after saline and frustration were consistently faster than for frustration trials with nicotine (Nf < Sf). A possible limitation of this study was the use of only two doses of nicotine. However, use of a higher nicotine dose (1.5 mg/kg) was precluded by observations of gross behavioral effects. The relationship between treatments, i.e., Nr = Sr < N f < Sf, was observed for both doses of nicotine used. If the effect of non-reward, in situations where the animals had been previously reinforced, caused frustration and this frustration, in turn, produced increased aggressiveness as quantified by faster running speeds, then it may be said that nicotine administration in the present study decreased the frustrationproduced increase in aggression when compared to control saline. The importance of these observations, on the effect of nicotine on aggressiveness, may be seen in the wide use of nicotine in tobacco smoking in humans. If smoking lowers hostility in humans, as indicated by recent investigations (Heimstra et al., 1967; Schechter and Rand, 1974), this may be a factor in the continuance of the smoking habit, and may be viewed as a 'beneficial' effect for a much-maligned habit.
References Amsel, A. and J. Roussel, 1952, Motivational properties of frustration. 1. Effect on a running response of the addition of frustration to the motivational complex, J. Exptl. Psychol. 43,363.
M.D. Schechter, Nicotine and rat's response to frustrative non-reward Azrin, N.H., R.R. Hutchinson and D.F. Hake, 1966, Extinction-induced aggression, J. Exptl. Anal. Behav. 9, 191. Crespi, L.P., 1944, Amount of reinforcement and level of performance, Psychol. Rev. 51, 341. Emley, G.S., R.R. Hutchinson and N.A. Hunter, 1971, Selective actions of morphine, chlorpromazine, chlordiazepoxide, nicotine and d-amphetamine on shock-produced aggressive and motor responses in the squirrel monkey, Federation Proc. 30,390. Heimstra, N.W., N.R. Bancroft and A.R. DeKock, 1967, Effect of smoking upon performance in a simulated driving task, Ann. N.Y. Acad. Sci. 142,295. Kostowski, W., 1968, A note on the effects of some cholinergic and anticholinergic drugs on the aggressive behaviour and spontaneous electrical activity of the central nervous system in the ant, Formica tufa, J. Pharm. Pharmacol. 20, 381.
315
Miller, N.E. and S.S. Stevenson, 1936, Agitated behaviour of rats during experimental extinction and a curve of spontaneous recovery, J. Comp. Psychol. 21,205. Schechter, M.D. and M.J. Rand, 1974, Effect of acute deprivation of smoking on aggression and hostility, Psychopharmacologia 35, 19. Silverman, A.P., 1970, A laboratory model for behaviour as an indicator of toxicity, in: Chemical influences on Behaviour, eds. R. Porter and J. Birch, Ciba Foundation Study Group No. 35 (J. and A. Churchill, London) p. 25. Thompson, T. and W. Bloom, 1966, Aggressive behaviour and extinction-induced response-rate increase, Psychonom. Sci. 5,335. Winer, B.J., 1962, Statistical Principles in Experimental Design (McGraw Hill New York, N.Y.).
Short communication EFFECT OF NICOTINE ON RESPONSE THE RAT
TO FRUSTRATIVE
NON-REWARD
IN
Martin D. SCHECHTER* Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia Received 27 August 1974, accepted 4 October 1974
M.D. SCHECttTER, Effect of nicotine on response to frustrative non-reward in the rat, European J. Pharmacol. 29 (1974) 312-315. Rats were subjected to frustrative non-reward in the Amsel double runway after administration of nicotine and saline. Results revealed that nicotine decreases the magnitude of the frustrative effect when compared to saline (p < 0.01). This finding is interpreted, in light of other studies reporting a decline in aggression after nicotine administration.
Nicotine
Aggression
Frustration
I. Introduction It is well established that, following a history of reinforcement on a well learned response, the onset of extinction produces an abrupt increase in the vigor of responding (Miller and Stevenson, 1936; Crespi, 1944). This increased vigor is thought to reflect a state o f aggression since it increases the tendency of the animal subject to attack other animals or objects in the experimental space (Azrin et al., 1966; Thompson and Bloom, 1966). Amsel and Roussel (1952) observed that when a running response in rats had been maximally elicited under hunger motivation, the addition o f non-reward resulted in the establishment of a new and higher maximum running speed. By comparing response rates (running speeds) immediately before and after the occurrence of non-reward, it was possible to quantify the behavioral effects (aggressiveness) of the extinction (frustration) operation. In the light of recent investigations reporting the ability o f nicotine to decrease various types of aggres* Supported by a grant from the American Medical Association Education and Research Foundation. Present address: Department of Pharmacology, Eastern Virginia Medical School, Norfolk, Virginia 23507, U.S.A.
Runway
Rat
siveness in rats (Silverman, 1970) squirrel monkeys (Emley et al., 1971), ants (Kostowski, 1968) and man (Schechter and Rand, 1974), the present study sought to investigate if nicotine would affect increased aggression as defined as the after-effect o f non-reinforcement in a previously reinforced response.
2. Materials and methods 2.1. Measurement o f running speeds 10 experimentally naive, female hooded rats, 120 days old at the beginning o f experimentation, were housed individually with free access to food and water until the fifth day of experimental adaptation. The apparatus consisted of a straight 247.3 cm plastic alley divided in the following order: a 30.5 cm long start box, 91.4 cm long runway, 30.5 cm goal box, a second 91.4 cm runway and second goal box. The inside dimensions o f the alley were 20.3 cm wide and 16.5 cm high. All areas were the same color and fitted with hinged transparent tops to facilitate viewing and removal. Retrace doors were used at the front of each goal box to insure that once the rat had en-
M.D. Schechter, Nicotine and rat's response to frustrative non-reward
tered the box it could not retreat. Manually operated guillotine doors served as exits from the start box and goal boxes. A photoelectric cell, mounted 4.3 cm from the floor, was located 13.9 cm from the guillotine door of the first goal box, in the first section of the second runway. When this light beam was broken, by the passing of the rat, a Yunker Electronics msec timer was activated. A second photoelectric cell was located 61 cm farther along the second runway at a point 7.6 cm from the retrace door of the second goal box, and when this light was interrupted the msec timer was stopped. Thus, the time to run 61 cm of the 91.4 cm long second runway could be measured in msec. 2.2. Procedure
Before formal training began, the rats underwent 10 days of adaptation to the experimental environment. The first 5 days were spent in adapting the rats to handling and free exploration of the apparatus. Each rat was handled for I0 min each day, and allowed 5 min in the apparatus with the partitioning doors opened and food placed in both goal boxes. During the next 5 days, the rats received only enough food in their home cages to maintain them at 80% body weight and each rat was trained io push open the retrace doors to gain admission to each goal box to obtain food. During training, each rat was injected s.c. with a constant volume of 1 ml/kg of saline (0.9% NaCI solution) and 15 min later, it was placed into the start box. The trial began with the opening of the guillotine door when the rat had oriented forward. The rat traversed the first runway, entered the first goal box and ate the food provided. After 15 sec access to the food, the guillotine door of the first goal box was raised and the rat negotiated the second runway and entered the second goal box to obtain the food provided. During this phase of the study, the following conditions were standard: 2 trials per day, one at 8 am and the second at 3 pm; saline administered 15 rain prior to the start of all trials; reinforcement, consisting of 4 0.05 g specially compounded food pellets, provided in both goal boxes; 15 sec retention time in the first goal box and running speeds in the second runway recorded. By the seventieth trial with saline administration
313
and food provided in both goal boxes, the running speeds for all rats had stabilized. The procedure was altered after trial 89 to consist of one of the following 4 treatments: (1) Saline reinforcement (Sr) - saline administration with food provided in both goal boxes; (2) Saline frustration (SO - saline administration with no food in the first goal box; (3) Nicotine reinforcement (Nr) - nicotine administration with food provided in both goal boxes: and (4) Nicotine frustration (N O - nicotine administration with no food provided in the first goal box. All injections were s.c. at a constant volume of I ml/kg body weight and each trial began 15 min post-injection. The administration sequence of the 4 treatments was randomized with all rats receiving 2 treatments per day. Retention time in the first goal box was 15 sec for both reinforcement and non-reinforcement trials and food always provided in the second goal box. The dosages of nicotine used, in 2 blocks of experiments, were 0.4 and 0.8 mg/kg with 0.9% saline used as vehicle and doses calculated as base. The data, in terms of mean running speeds for each rat in the second runway, were analyzed by analysis of variance. When the level of significance of the withinsubject statistic exceeded p < 0 . 0 1 , the NewmanKeul's test on differences between pairs of means (Winer, 1962)was applied to evaluate levels of significance between specific treatments, i.e.,Nr vs. St', Sr vs. Sf, Nf vs. Sf, Nr vs. St, Nr vs. Nf, Nf vs. Sr, at each dose level of nicotine used.
3. Results Frustration is measured in the double runway as increased running speed in runway 2 on those trials in which reinforcement is omitted from goal box 1. Table 1 presents mean running speeds under the various experimental conditions. Analysis of the data, by evaluating the mean running speed of each of 10 rats in each condition, revealed that a statistically significant difference exists between the 4 conditions after 0.4 mg/kg nicotine (F = 62.85; df = 3/27;p < 0.01); and after 0.8 mg/kg nicotine (F = 64.93; df = 3/27; p <0.01). Evaluation of the data by the Newman-Keul's test on differences between pairs of means for each treatment shows that there was a significant difference
314
M.D. Schechter, Nicotine and rat's response to frustrative non-reward
Table 1 Mean running times in runway 2 for four treatments. Treatment: nicotine dose (mg/kg)
Nr
Sr
Nf
Sf
No. of trials for each treatment
F-value2
df
0.4 0.8
882.71 892.3
881.2 891.8
873.4 879.4
866.8 860.4
8 4
62.85 64.93
3/27 3/27
l Each value is the mean running time in msec of 10 rats in the number of trials for each treatment. 2F-value is the within-subject statistic derived by analysis of variance; in both eases p < 0.01.
( p < 0 . 0 1 ) between all treatments except those between Sr and Nr. Thus, the relationship of running speeds, at both doses of nicotine, for the treatments given is Nr = Sr < Nf < Sf. Nicotine administration had no effect on running speeds when compared to saline in the reinforcement trials, whereas, frustrative non-reward trials produced significantly faster running speeds when compared to reinforcement trials, with the administration of both saline and nicotine. The administration of both doses of nicotine produced significantly slower mean running speeds under frustrative non-reward than did the administration of saline.
4. Discussion The results of this study confirm the observations reported by Amsel and Roussel (1952) to prove the 'frustrative non-reward' theory. The mean running speed of the 10 rats before nicotine administration and frustrative trials was 881.5 msec, and the mean running speed for Sr trials during the first trial block with 0.4 mg/kg nicotine remained at 881.2 msec. The initiation of frustration trials after saline administration (SO produced an increase in mean running speed to 866.8 msec. Thus, the maximally elicited running speed after saline and reinforcement was shown to increase to a new and higher maximum running speed by the addition of frustration to the motivational complex. The administration of nicotine, at doses of 0.4 and 0.8 mg/kg was shown to be unable to block the effect of frustrative non-reward on running speed, i.e., the mean running speeds with nicotine and reinforcement were always significantly more than with nicotine and
frustration (Nr < Nf). Nicotine had no effect on mean running speeds during reinforcement trials when compared with saline (Nr = Sr). However, running speeds after saline and frustration were consistently faster than for frustration trials with nicotine (Nf < Sf). A possible limitation of this study was the use of only two doses of nicotine. However, use of a higher nicotine dose (1.5 mg/kg) was precluded by observations of gross behavioral effects. The relationship between treatments, i.e., Nr = Sr < N f < Sf, was observed for both doses of nicotine used. If the effect of non-reward, in situations where the animals had been previously reinforced, caused frustration and this frustration, in turn, produced increased aggressiveness as quantified by faster running speeds, then it may be said that nicotine administration in the present study decreased the frustrationproduced increase in aggression when compared to control saline. The importance of these observations, on the effect of nicotine on aggressiveness, may be seen in the wide use of nicotine in tobacco smoking in humans. If smoking lowers hostility in humans, as indicated by recent investigations (Heimstra et al., 1967; Schechter and Rand, 1974), this may be a factor in the continuance of the smoking habit, and may be viewed as a 'beneficial' effect for a much-maligned habit.
References Amsel, A. and J. Roussel, 1952, Motivational properties of frustration. 1. Effect on a running response of the addition of frustration to the motivational complex, J. Exptl. Psychol. 43,363.
M.D. Schechter, Nicotine and rat's response to frustrative non-reward Azrin, N.H., R.R. Hutchinson and D.F. Hake, 1966, Extinction-induced aggression, J. Exptl. Anal. Behav. 9, 191. Crespi, L.P., 1944, Amount of reinforcement and level of performance, Psychol. Rev. 51, 341. Emley, G.S., R.R. Hutchinson and N.A. Hunter, 1971, Selective actions of morphine, chlorpromazine, chlordiazepoxide, nicotine and d-amphetamine on shock-produced aggressive and motor responses in the squirrel monkey, Federation Proc. 30,390. Heimstra, N.W., N.R. Bancroft and A.R. DeKock, 1967, Effect of smoking upon performance in a simulated driving task, Ann. N.Y. Acad. Sci. 142,295. Kostowski, W., 1968, A note on the effects of some cholinergic and anticholinergic drugs on the aggressive behaviour and spontaneous electrical activity of the central nervous system in the ant, Formica tufa, J. Pharm. Pharmacol. 20, 381.
315
Miller, N.E. and S.S. Stevenson, 1936, Agitated behaviour of rats during experimental extinction and a curve of spontaneous recovery, J. Comp. Psychol. 21,205. Schechter, M.D. and M.J. Rand, 1974, Effect of acute deprivation of smoking on aggression and hostility, Psychopharmacologia 35, 19. Silverman, A.P., 1970, A laboratory model for behaviour as an indicator of toxicity, in: Chemical influences on Behaviour, eds. R. Porter and J. Birch, Ciba Foundation Study Group No. 35 (J. and A. Churchill, London) p. 25. Thompson, T. and W. Bloom, 1966, Aggressive behaviour and extinction-induced response-rate increase, Psychonom. Sci. 5,335. Winer, B.J., 1962, Statistical Principles in Experimental Design (McGraw Hill New York, N.Y.).