Evaluation of the reinforcing and discriminative stimulus effects of cocaine in combination with (+)-AJ 76 or clozapine

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 266; no. 2; pp. 780 - 789
• Main Authors: VANOVER, K. E, PIERCEY, M. F, WOOLVERTON, W. L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 1993
• Subjects: Biological and medical sciences; Drug addictions; Macaca mulatta; Medical sciences; Toxicology; Drug addiction; Operant conditioning; Neuroleptic; Psychotropic; Dopamine receptor; Monkey; Self administration; Vertebrata; Mammalia; Acquisition process; Animal; Primates; Cocaine; Drug of abuse; Stimulus discrimination
• ISSN: 0022-3565; 1521-0103

The present study was designed to evaluate the effects of the putative dopamine autoreceptor antagonist (+)-AJ 76 (AJ) or the atypical antipsychotic clozapine (CLZ) on the reinforcing and discriminative stimulus effects of cocaine in monkeys. One group of rhesus monkeys (n = 6) was allowed to self-administer cocaine (0.03 or 0.1 mg/kg/injection i.v., fixed-ratio 10, 2 hr/day). A second group of monkeys (n = 5) was trained to discriminate cocaine (0.2 or 0.4 mg/kg i.m., 10 min presession) from saline in a two lever, food-reinforced, drug discrimination paradigm. When behavior was stable, AJ or CLZ was administered i.m., 15 or 30 min presession. Intermediate doses of both compounds (1.0-3.0 mg/kg of AJ; 0.3-1.0 mg/kg of CLZ) increased cocaine self-administration, while responding remained evenly distributed over the session. A higher dose of CLZ decreased cocaine self-administration in an apparently nonspecific manner. When combined with saline, partial substitution for cocaine was seen in one of three monkeys with AJ and in none with CLZ. In combination with the training dose of cocaine in the discrimination experiment, both AJ and CLZ decreased drug appropriate responding by at least 50% in two of four monkeys, but had little or no effect in the other monkeys up to doses that completely suppressed lever pressing (6.4 mg/kg of AJ; 3.2 mg/kg of CLZ).