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.