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  • Title: Clozapine promotes approach-oriented behavior in male mice.
    Author: Dixon AK, Huber C, Lowe DA.
    Journal: J Clin Psychiatry; 1994 Sep; 55 Suppl B():4-7. PubMed ID: 7961571.
    Abstract:
    Clozapine, an atypical antipsychotic agent, exerts ameliorative effects upon negative symptoms, but to date, its mechanism of action is poorly understood. We employed ethological methods to study the effects of clozapine, given 1 hour beforehand, on the social responses of (1) an individually housed male mouse exposed to an equally "matched" aggressive male opponent and (2) a group-housed "intruder" mouse exposed to an isolated, aggressive male. Encounters lasted 6 minutes. In matched pairs, mice given clozapine (0.01, 0.03, or 0.1 mg/kg s.c.) showed a significant increase in aggression without signs of stimulation. When given to intruder mice, clozapine (0.03, 0.1, or 0.3 mg/kg p.o.) markedly reduced defensive behavior and reinstated their investigative and sexual activities. The results suggest that low, nonsedating doses of clozapine counteract social withdrawal by selectively increasing "situationally appropriate" approach behavior.
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