Chlorpromazine effects on cocaine-reinforced responding in rhesus monkeys: reciprocal modification of rate-altering effects of the drugs
Herling, S.; Woods, J.H.
Journal of Pharmacology and Experimental Therapeutics 214(2): 354-361
1980
ISSN/ISBN: 0022-3565 PMID: 6771394 Document Number: 160633
The effects of i.m. injections of chlorpromazine were studied in rhesus monkeys whose lever-press responding was maintained under a 2nd-order fixed-interval, fixed-ratio schedule of food (300 mg) or cocaine (0.01-0.3 mg/kg per injection) reinforcement. When the dose per injection of cocaine was small (0.01-0.03 mg/kg), chlorpromazine produced similar dose-related decreases in responding maintained by cocaine or food. As the dose of cocaine that maintained behavior was increased, the effects of chlorpromazine were correspondingly attenuated, suggesting a dose-related antagonism by self-injected cocaine of the rate-decreasing effects of chlorpromazine. When high doses of cocaine (0.1-0.3 mg/kg per injection) maintained responding, chlorpromazine reversed, to some extent, the changes in the rate and pattern of responding produced by self-injected cocaine. When self-injections of high doses of cocaine induced relatively low rates of behavior, chlorpromazine increased cocaine-reinforced responding. An analysis of the effects of chlorpromazine on response rates in successive segments of the fixed interval revealed that the ability of the drug to increase low rates of responding maintained by cocaine could not be attributed solely to the rate-dependent effects of chlorpromazine. The behavioral effects of combinations of cocaine and chlorpromazine appear to involve a reciprocal antagonism of the rate-modifying effects of the drugs.