The comparative effects of clozapine versus haloperidol on initiation and maintenance of alcohol drinking in male alcohol-preferring P rat

Abstract Alcohol use disorder, characterized by modest levels of alcohol use, commonly occurs in patients with schizophrenia and dramatically worsens their course. Recent data indicate that the atypical antipsychotic clozapine, but not the typical antipsychotic haloperidol, decreases alcohol drinking both in patients with schizophrenia and also in the Syrian golden hamster, an animal model of moderate alcohol drinking. The present study was designed to assess the comparative effects of clozapine and haloperidol in the alcohol-preferring (P) rat, an animal model of alcoholism. First, the study investigated the comparative effects of clozapine and haloperidol on initiation of alcohol consumption in P rats, which models the early stage of alcoholism. Second, the study assessed the comparative effects of clozapine and haloperidol on maintenance of chronic alcohol consumption in P rats to provide a clue as to whether either drug may also limit alcohol consumption in alcohol-dependent patients. Clozapine attenuated the initiation of alcohol drinking and development of alcohol preference while haloperidol did not. However, neither clozapine nor haloperidol attenuated maintenance of chronic alcohol drinking. Taken together, the current data suggest that clozapine, but not haloperidol, may be effective at reducing alcohol abuse or non-dependent drinking and the P rat, used within an alcohol initiation paradigm, and may differentiate the effects of clozapine and haloperidol on alcohol drinking.