title: Raclopride lessens the ability of clozapine to suppress alcohol drinking in Syrian golden hamsters.
abstract: Emerging evidence suggests that the atypical antipsychotic clozapine decreases alcohol consumption in patients with schizophrenia, while typical antipsychotics, all of which are potent dopamine (DA) D2 receptor antagonists, do not. We have proposed that clozapine, through its weak DA D2 receptor blocking action, coupled with its ability to potentiate noradrenergic and serotonergic activity, may ameliorate a dysfunction in the mesocorticolimbic DA reward circuitry that underlies alcohol use disorder in patients with schizophrenia. In prior studies, we have demonstrated that clozapine also decreases alcohol drinking in the Syrian golden hamster, but haloperidol does not. The purposes of the current study were: (1) to further assess the effect of clozapine (2 or 4 mg/kg/day, s.c.) on alcohol consumption in hamsters, using a continuous access, 2-bottle choice paradigm; and (2) to examine whether clozapine's effect on alcohol drinking is affected by increasing its DA D2 blockade through adjunctive use of the potent DA D2 receptor antagonist raclopride (2, 4, or 6 mg/kg/day, s.c.). The major findings were: (1) clozapine suppressed both initiation and maintenance of alcohol drinking in hamsters; and (2) these effects of clozapine were lessened when raclopride was given adjunctively with clozapine. These data suggest that clozapine may limit alcohol drinking in the golden hamster (and possibly in patients with schizophrenia) in part because of its weak blockade of the DA D2 receptor.
authors.affiliation: Department of Psychiatry, Dartmouth Medical School, Lebanon, NH 03576, USA. david.t.chau@dartmouth.edu
authors.forename: David T
authors.initials: DT
authors.lastname: Chau
authors.forename: Jayme
authors.initials: J
authors.lastname: Ahmed
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Wang
authors.forename: Haiyi
authors.initials: H
authors.lastname: Xie
authors.forename: Ree
authors.initials: R
authors.lastname: Dawson
authors.forename: Alan I
authors.initials: AI
authors.lastname: Green
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D003024:Clozapine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D006224:Cricetinae; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D020891:Raclopride / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D020891:Raclopride; D003024:Clozapine