Discriminative stimulus properties of clozapine and chlorpromazine.

Rats were trained to discriminate pairs of drug states in a two-lever operant paradigm for food reinforcement. One group learned to discriminate clozapine from vehicle, a second group learned to discriminate chlorpromazine from vehicle, and a third group learned to discriminate clozapine from chlorpromazine. The result that the clozapine versus chlorpromazine discrimination was acquired, as well as the results of substitution tests with non-training drugs, suggest that the stimulus properties of the classical neuroleptics and other psychotherapeutic agents indicate that the stimulus properties of antipsychotics are distinct from other classes of psychotropic agents, and support the hypothesis that clozapine may be a unique antipsychotic. It is suggested that the unique discrimination stimulus produced by clozapine may be related to the differential effect of the drug on the extrapyramidal versus accumbens dopamine system.