Behavioral effects of clozapine: comparison with thioridazine, chlorpromazine, haloperidol and chlordiazepoxide in squirrel monkeys

The behavioral effects of the antipsychotic drug, clozapine, were compared with those of thioridazine, chlorpromazine, haloperidol and chlordiazepoxide. Behavior of squirrel monkeys was controlled by different consequences of a lever-pressing response (presentation of food, presentation of electric shock or termination of a stimulus associated with electric shock) under different schedules of reinforcement (a fixed-interval schedule or a multiple schedule with alternating fixed-ratio and fixed-interval components). The effects of thioridazine (0.2-24.6 mumol/kg), chlorpromazine (0.03-2.8 mumol/kg) and haloperidol (0.001-0.08 mumol/kg) were largely independent of the type of schedule or the type of consequent event that maintained responding: each drug produced dose-related decreases in responding under all conditions in which they were studied. Clozapine (0.1-9.2 mumol/kg) and chlordiazepoxide (0.9-167.4 mumol/kg) also only decreased responding under most schedule conditions; however, intermediate doses of either drug markedly increased responding maintained by presentation of food under the fixed-interval schedule (whether programmed singly or as a component of the multiple schedule). Only clozapine increased responding maintained by presentation of electric shock under the fixed-interval schedule. Thus, the behavioral effects of clozapine differed qualitatively from those of representative antipsychotic and antianxiety drugs.