Abstract
Previous work has shown that administration of pimozide and other neuroleptic drugs can produce within-session response decrement patterns of appetitively-reinforced behaviour. This phenomenon has been described as an extinction-like pattern of responding and used as evidence for the hypothesis that these drugs attenuate the rewarding properties of food, water and electrical stimulation of the brain. The present study was carried out to investigate within-session patterns of responding maintained by food presentation or shock avoidance after administration of a variety of neuroleptic and non-neuroleptic drugs. Haloperidol, metoclopramide, pimozide and butaclamol produced within-session response decrements of both food-reinforced lever pressing and one-way shock avoidance. The atypical antipsychotic drug clozapine did not consistently produce similar effects nor did the α-adrenoceptor agonist clonidine, the opiate agonist morphine, the benzodiazepine anxiolytic chlordiazepoxide and the muscle relaxant methocarbamol, although all these drugs were tested up to doses which markedly disrupted responding. Thus, within-session response decrement patterns are a characteristic effect of dopamine-blocking neuroleptic drugs. However, because of the generally similar effects of these drugs on appetitively-and aversively-motivated behaviour, these effects are probably best interpreted as actions on motor, rather than motivational, mechanisms.
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References
Anisman H, Corradini A, Tombaugh TN, Zacharko RM (1982) Avoidance performance, cue and response-choice discrimination after neuroleptic treatment. Pharmacol Biochem Behav 17:1245–1249
Arnt J (1982) Pharmacological specificity of conditioned avoidance response inhibition in rats: inhibition by neuroleptics and correlation to dopamine receptor blockade. Acta Pharmacol Toxicol 51:321–329
Atrens DM, Ljungberg T, Ungerstedt U (1976) Modulation of reward and aversion processes in the rat diencephalon by neuroleptics: differential effects of clozapine and haloperidol. Psychopharmacology 49:97–100
Bacotti AV (1981) Clozapine effects on responding maintained under shock presentation and shock termination schedules. Pharmacol Biochem Behav 15:415–418
Barrett JE (1982) Effects of clozapine, haloperidol and thiothixene on schedule-controlled responding and schedule-induced eating and drinking in rabbits. Pharmacol Biochem Behav 17:1049–1053
Beninger RJ, Mason ST, Phillips AG, Fibiger HC (1980) The use of conditioned suppression to evaluate the nature of neuroleptic induced avoidance deficits. J Pharmacol Exp Ther 213:623–627
Beninger RJ, Phillips AG, Fibiger HC (1983) Prior training and intermittent retraining attenuate pimozide-induced avoidance deficits. Pharmacol Biochem Behav 18:619–624
Carlton PL (1983) A primer of behavioral pharmacology. WH Freeman, New York
Cook L, Weidley E (1957) Behavioral effects of some psychopharmacological agents. Ann NY Acad Sci 66:740–752
Davidson AB, Weidley E (1976) Differential effects of neuroleptic and other psychotropic agents on acquisition of avoidance in rats. Life Sci 18:1279–1284
Dwoskin LP, Sparber SB (1983) Comparison of yohimbine, mianserin, chlorpromazine and prazosin as antagonists of the suppressant effect of clonidine on operant behavior. J Pharmacol Exp Ther 226:57–64
Evenden JL, Robbins TW (1983) Dissociable effects of d-amphetamine, chlordiazepoxide and α-flupenthixol on choice and rate measure of reinforcement in the rat. Psychopharmacology 79:180–186
Faustman WO, Fowler SC (1982) An examination of methodological refinements, clozapine and fluphenazine in the anhedonia paradigm. Pharmacol Biochem Behav 17:987–993
Fenton HM, Liebman JM (1982) Self-stimulation response decrement patterns differentiate clonidine, baclofen and dopamine antagonists from drugs causing performance deficit. Pharmacol Biochem Behav 17:1207–1212
Fibiger HC, Zis AP, Phillips AG (1975) Haloperidol induced disruption of conditioned avoidance responding: attenuation by prior training or by anticholinergic drugs. Eur J Pharmacol 30:309–314
Fouriezos G, Wise RA (1976) Pimozide-induced extinction of intracranial self-administration: Response patterns rule out motor or performance deficits. Brain Res 103:377–380
Fouriezos G, Hansson P, Wise RA (1978) Neuroleptic-induced attenuation of brain stimulation reward in rats. J Comp Physiol Psychol 92:661–671
Fowler SC, Ford KE, Gramling SE, Nail GL (1984) Acute and subchronic effects of neuroleptics on qualitative measures of discriminative motor control in rats. Psychopharmacology 84:368–373
Gerber GJ, Sing J, Wise RA (1981) Pimozide attenuates lever pressing for water reinforcement in rats. Pharmacol Biochem Behav 14:201–205
Greenshaw AJ, Sanger DJ, Blackman DE (1981) The effects of pimozide and of reward omission on fixed-interval behavior of rats maintained by food and electrical brain stimulation. Pharmacol Biochem Behav 15:227–233
Hayashi T, Tadokoro S, Hashimoto H, Nakashima M (1982) Enhancement of avoidance-suppressing effect after repeated administration of haloperidiol and serum haloperidol in rats. Pharmacol Biochem Behav 17:131–136
Kuribara H, Tadokoro S (1981) Correlation between anti-avoidance activities of antipsychotic drugs in rats and daily clinical doses. Pharmacol Biochem Behav 14:181–192
Leander JD (1975) Rate-dependent effects of drugs II. Effects of some major tranquilizers on multiple fixed-ratio, fixed-interval schedule performance. J Pharmacol Exp Ther 193:689–700
Liebman J (1982) Understanding neuroleptics: From “anhedonia” to “neuroleptothesia”. Behav Brain Sci 5:64–65
Mason ST, Beninger RJ, Fibiger HC, Phillips AG (1980) Pimozide-induced suppression of responding: Evidence against a block of food reward. Pharmacol Biochem Behav 12:917–923
McCleary PE, Leander JD (1981) Clonidine analgesia and suppression of operant responding: Dissociation of mechanism. Eur J Pharmacol 69:63–69
Migler B (1975) Conditioned approach: an analogue of conditioned avoidance; effects of chlorpromazine and diazepam. Pharmacol Biochem Behav 3:961–965
Monti JM, Hance AJ (1967) Effects of haloperidol and trifluperidol on operant behavior in the rat. Psychopharmacologia 12:34–43
Morley MJ, Bradshaw CM, Szabadi E (1984) The effect of pimozide on variable-interval performance: A test of the ‘anhedonia’ hypothesis of the mode of action of neuroleptics. Psychopharmacology 84:531–536
Morpurgo C (1965) Drug-induced modifications of discriminated avoidance behavior in rats. Psychopharmacologia 8:91–99
Phillips AG, Fibiger HC (1979) Decreased resistance to extinction after haloperidol: implications for the role of dopamine in reinforcement. Pharmacol Biochem Behav 10:751–760
Posluns D (1962) An analysis of chlorpromazine-induced suppression of the avoidance response. Psychopharmacologia 3:361–373
Ray OS, Bivens LW (1967) Phenothiazine depression of approach and avoidance behavior. Psychopharmacologia 10:196–203
Sanger DJ (1985) The effects of clozapine on shuttle-box avoidance responding in rats: Comparisons with haloperidol and chlordiazepoxide. Pharmacol Biochem Behav 23:231–236
Spealman RD, Katz JL (1980) Some effects of clozapine on punished responding by mice and squirrel monkeys. J Pharmacol Exp Ther 212:435–440
Spealman RD, Kelleher RT, Goldberg SR, DeWeese J, Goldberg DM (1983) Behavioral effects of clozapine: comparison with thioridazine, chlorpromazine, haloperidol and chlordiazepoxide in squirrel monkeys. J Pharmacol Exp Ther 224:127–134
Stille G, Lauener H, Eichenberger E (1971) The pharmacology of 8-chloro-11(4-methyl-l-piperazinyl)-5H-dibenzo [b,e]diazepine (clozapine). Il Farmaco 26:603–625
Tombaugh TN, Anisman H, Tombaugh J (1980) Extinction and dopamine receptor blockade after intermittent reinforcement training: Failure to observe functional equivalence. Psychopharmacology 70:19–28
Wise RA (1982) Neuroleptics and operant behavior: The anhedonia hypothesis. Behav Brain Sci 5:39–87
Wise RA, Spindler J, Legault L (1978) Major attenuation of food reward with performance-sparing doses of pimozide in the rat. Can J Psychol 32:77–85
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Sanger, D.J. Response decrement patterns after neuroleptic and non-neuroleptic drugs. Psychopharmacology 89, 98–104 (1986). https://doi.org/10.1007/BF00175198
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DOI: https://doi.org/10.1007/BF00175198