The interaction of clozapine with the metachlorophenylpiperazine (mCPP) discriminative stimulus |
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| Institution: | 1. National and Kapodistrian University of Athens, School of Medicine, First Department of Psychiatry, Eginition Hospital, 74 Vas. Sofias Avenue, 11528 Athens, Greece;2. University Department of Psychiatry, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, United Kingdom;3. University Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa;1. University of Maryland School of Pharmacy, 20 N Pine St, Baltimore, MD 21201, USA;2. Maryland Psychiatric Research Center, University of Maryland School of Medicine, PO Box 21247, Catonsville, MD 21228, USA |
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| Abstract: | The psychotropic effects of the 5-HT2C agonist mCPP in human subjects are blocked by the atypical antipsychotic clozapine, but not by typical antipsychotics. An understanding of the mechanistic basis for the interaction of clozapine and mCPP would provide further insight into the basis for its unique therapeutic effects in humans. Drug-induced stimulus control provides an animal model for the subjective effects of psychotropic agents in humans. In the present study, the interaction of the atypical antipsychotic clozapine and the typical antipsychotic fluphenazine with the mCPP-stimulus were defined. Neither drug antagonized the stimulus effects of mCPP in vivo. In contrast, clozapine fully antagonized the mCPP-stimulated phosphoinositide turnover at the 5-HT2C receptor in vitro. The present data indicate that the paradigm of mCPP-induced stimulus control does not facilitate the differentiation of atypical and typical antipsychotic activities. |
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