Acute effects of neuroleptics on brain self-stimulation thresholds in rats

The acute effects of 5 neuroleptic drugs were tested in rats implanted with stimulating electrodes in the medial forebrain bundle and trained in a brain self-stimulation threshold procedure. Haloperidol (0.01-0.10 mg/kg) and loxapine (0.03-0.56 mg/kg) produced increases in reinforcement thresholds accompanied by reductions in response rates. Chlorpromazine (0.10-3.0 mg/kg) did not significantly alter reinforcement thresholds, but did produce dose-dependent reductions in response rates. Pimozide (0.1-1.75 mg/kg) was similar to chlorpromazine and significantly increased the reinforcement threshold only at the highest dose, although a graded decrease in response rates occurred over a wide dose-range. Clozapine (0.1-1.75 mg/kg) increased reinforcement thresholds without producing any significant changes in response rates, but when 3.0 mg/kg was administered, a marked disruption of behavior occurred. The results suggested that a distinction can be made between the effects of neuroleptics on motor behavior and on central reinforcement thresholds, and this may help in the interpretation of the relation between the chemical and clinical potency of antipsychotic drugs.