Differential tolerance to the behavioral effects of chronic pimozide and clozapine on multiple random interval responding in rats

The behavioral effects of 10 days of chronic administration of the typical neuroleptic, pimozide, and the atypical neuroleptic, clozapine, were compared on a schedule of multiple random interval responding for food reinforcement and on photocell activity in rats. The low doses of both neuroleptics (0.125mg/kg pimozide, 1.25mg/kg clozapine) had little effect on any of the dependent variables measured. The high doses (1.0mg/kg pimozide, 10.0mg/kg clozapine) significantly disrupted response rates and reinforcement rates and significantly increased response duration when the drugs were first administered. Chronic administration, however, resulted in different profiles for the two drugs. While tolerance developed to the disruptive effects of clozapine, tolerance did not develop to the disruptive effects of pimozide and, on some dependent measures, an increased sensitivity developed. No tolerance developed to the disruptive effects of either drug on photocell activity. The effects of the drugs depended on the reinforcement density of the operant schedule.