Clozapine increases breaking points on a progressive-ratio schedule reinforced by intravenous cocaine.
The effect of the atypical neuroleptic clozapine on cocaine self-administration reinforced on a progressive-ratio schedule in rats was examined. The rat's first response on a lever each day produced an IV infusion of cocaine (0.6 mg/injection) after which the requirements of the schedule escalated with each infusion until the frequency of responding on the lever fell below a criterion level. The final ratio completed was defined as the breaking point. Doses of 5 and 20 mg/kg clozapine produced either no effect or a nonspecific disruption in responding. Rats pretreated with 10 mg/kg clozapine responded to significantly higher breaking points, indicating an increased motivation to self-administer cocaine.
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Department of Psychology, Carleton University, Ottawa, Ontario, Canada.
Fitch
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Vickers
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Roberts
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D000818:Animals; D003024:Clozapine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration; D012701:Serotonin / Q000502:physiology
D012701:Serotonin; D003042:Cocaine; D003024:Clozapine; D004298:Dopamine