CLOZAPINE PROMOTES APPROACH-ORIENTED BEHAVIOR IN MALE-MICE

Clozapine, an atypical antipsychotic agent, exerts ameliorative effect s upon negative symptoms, but to date, its mechanism of action is poor ly 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'' aggr essive male opponent and (2) a group-housed ''intruder'' mouse exposed to an isolated, aggressive male. Encounters lasted 6 minutes. In matc hed 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. Wh en given to intruder mice, clozapine (0.03, 0.1, or 0.3 mg/kg p.o.) ma rkedly reduced defensive behavior and reinstated their investigative a nd sexual activities. The results suggest that low, nonsedating doses of clozapine counteract social withdrawal by selectively increasing '' situationally appropriate'' approach behavior.