title: Clozapine chronically suppresses alcohol drinking in Syrian golden hamsters.
abstract: Alcohol use disorder is common in patients with schizophrenia and is associated with poor clinical outcomes. Preliminary reports from our group and others suggest that the atypical antipsychotic clozapine may decrease alcohol use in these patients. We have previously shown that clozapine suppresses alcohol consumption for 9 days in Syrian golden hamsters. Here, we assessed the effects of clozapine on alcohol consumption in hamsters over a 27-day period, using a continuous access, 2-bottle (15% alcohol vs. water) protocol. Clozapine (4, 8, or 12 mg/kg/day, injected subcutaneously [s.c.]) dose-dependently suppressed alcohol drinking, while increasing food and water intake. There was no tolerance within individual groups to the effect of clozapine on alcohol drinking over time. In a separate experiment, the effects of clozapine on sucrose and water drinking and food intake over a 9-day period were assessed. Clozapine (4, 8, or 12 mg/kg/day s.c.) failed to suppress sucrose (0.09 M), food, or water consumption at any time-point tested. In a related study, assessment of blood alcohol levels in hamsters indicated that blood alcohol levels were maintained within a narrow and moderate range (7-13 mg/dL), levels noted by others to produce physiologic effects in rodents. The ability of clozapine to suppress alcohol drinking in the hamster over an extended period of time without suppressing sucrose, water, or food consumption is consistent with preliminary reports indicating that clozapine limits frequent alcohol use, even producing abstinence in many patients with schizophrenia.
authors.affiliation: Department of Psychiatry, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Chau
authors.forename: Danielle
authors.initials: D
authors.lastname: Gulick
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 / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D006224:Cricetinae; D019422:Dietary Sucrose / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D013997:Time Factors; D014867:Water / Q000008:administration & dosage
chemical_list: D014150:Antipsychotic Agents; D019422:Dietary Sucrose; D011619:Psychotropic Drugs; D014867:Water; D000431:Ethanol; D003024:Clozapine