Garmendia L, Sánchez J R, Azpiroz A, Brain P F, Simón V M
Dpto. de Procesos Psicológicos Básicos. Area de Psicobiología, Facultad de Psicología, Universidad del Pais Vasco, San Sebastian, Spain.
Physiol Behav. 1992 Jan;51(1):51-4. doi: 10.1016/0031-9384(92)90202-d.
Clinical studies have shown clozapine to be effective in the treatment of schizophrenia and associated with an extremely low incidence of extrapiramidal side effects. Diverse studies indicate that clozapine is an atypical neuroleptic with a preferential activity on the mesolimbic structures and a lower affinity for striatal D2 receptors than the classical antipsychotics. The purpose of this study was to assess the behavioral properties of clozapine, especially its effects on aggressive and motor behaviors. Individually housed male mice of the OF1 strain were exposed to anosmic "standard opponents" 30 minutes after the last drug administration. One category of animals received a single IP dose of the compound (0.2, 0.5, 1 or 1.5 mg/kg). Another category received daily doses (0.5, 1 or 1.5 mg/kg) for 21 days. Encounters were videotaped and behavior evaluated using an ethologically based analysis. Clozapine, in the acute treatment condition, produced a significant decrease in "attack" and "threat" behaviors without "immobility" being significantly increased. These results suggest a rather specific antiaggressive action of the compound with little motor impairment. In the chronic administration, no significant change in aggressive behavior was observed which may be attributed to the development of some degree of tolerance.
临床研究表明，氯氮平对精神分裂症的治疗有效，且锥体外系副作用的发生率极低。多项研究表明，氯氮平是一种非典型抗精神病药物，对中脑边缘结构具有优先活性，与经典抗精神病药物相比，对纹状体D2受体的亲和力较低。本研究的目的是评估氯氮平的行为特性，尤其是其对攻击行为和运动行为的影响。在最后一次给药30分钟后，将单独饲养的OF1品系雄性小鼠暴露于无嗅觉的“标准对手”面前。一类动物接受单次腹腔注射该化合物（0.2、0.5、1或1.5毫克/千克）。另一类动物连续21天接受每日剂量（0.5、1或1.5毫克/千克）。对相遇过程进行录像，并使用基于行为学的分析方法评估行为。在急性治疗条件下，氯氮平显著减少了“攻击”和“威胁”行为，而“不动”行为并未显著增加。这些结果表明该化合物具有相当特异性的抗攻击作用，且运动损伤较小。在慢性给药过程中，未观察到攻击行为有显著变化，这可能归因于某种程度的耐受性的形成。
