Dixon A K, Huber C, Lowe D A
Sandoz Research Institute Berne Ltd., Berne, Switzerland.
J Clin Psychiatry. 1994 Sep;55 Suppl B:4-7.
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.
氯氮平是一种非典型抗精神病药物，对阴性症状有改善作用，但迄今为止，其作用机制尚不清楚。我们采用行为学方法研究预先1小时给予氯氮平对以下两种情况社交反应的影响：（1）单独饲养的雄性小鼠暴露于同样“匹配”的具有攻击性的雄性对手；（2）群居的“入侵者”小鼠暴露于单独的具有攻击性的雄性小鼠。相遇持续6分钟。在配对的小鼠中，给予氯氮平（0.01、0.03或0.1毫克/千克，皮下注射）的小鼠攻击性显著增加且无兴奋迹象。当给予“入侵者”小鼠氯氮平时（0.03、0.1或0.3毫克/千克，口服），可显著减少防御行为并恢复其探究和性行为。结果表明，低剂量、无镇静作用的氯氮平通过选择性增加“情境适宜”的接近行为来抵消社交退缩。
