THE INTERACTION OF CLOZAPINE WITH THE METACHLOROPHENYLPIPERAZINE (MCPP) DISCRIMINATIVE STIMULUS

The psychotropic effects of the 5-HT2C agonist mCPP in human subjects are blocked by the atypical antipsychotic clozapine, but not by typica l antipsychotics. An understanding of the mechanistic basis for the in teraction of clozapine and mCPP would provide further insight into the basis for its unique therapeutic effects in humans. Drug-induced stim ulus control provides an animal model for the subjective effects of ps ychotropic agents in humans. In the present study, the interaction of the atypical antipsychotic clozapine and the typical antipsychotic flu phenazine with the mCPP-stimulus were defined. Neither drug antagonize d the stimulus effects of mCPP in vivo. In contrast, clozapine fully a ntagonized the mCPP-stimulated phosphoinositide turnover at the 5-HT2C receptor in vitro. The present data indicate that the paradigm of mCP P-induced stimulus control does not facilitate the differentiation of atypical and typical antipsychotic activities.