Clozapine is thought to induce obsessive compulsive symptoms (OCS) in schizophrenic patients. However, because OCS are often comorbid with schizophrenia regardless of clozapine treatment, it remains unclear whether clozapine can generate OCS de novo. Thus, it has been difficult to establish a causal link between clozapine and OCS in human studies. To address this question, we asked whether chronic treatment with clozapine can induce obsessive compulsive disorder (OCD)-like behavior in mice. We injected mice with long-term continuous release pellets embedded with clozapine four times at 60-day intervals and then monitored the mice for signs of OCD-like behavior up to 40 wk. of age. We found clozapine increases grooming behavior as early as 30 wk. of age. We also investigated the effect clozapine on grooming behavior in Sapap3 knockout (KO) mice, which are a well-known animal model of OCD. In Sapap3 heterozygous KO mice, clozapine increases grooming behavior much earlier than in wild-type mice, suggesting a clozapine-OCD gene interaction. Fluoxetine, which is often used in the treatment of OCS and OCD, reduced the grooming behavior induced by clozapine. These data demonstrate that chronic clozapine treatment can generate OCD-like behavior in mice and support the hypothesis that clozapine produces de novo OCS regardless of schizophrenia status.

中文翻译：

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氯氮平在小鼠中产生强迫症样行为。

氯氮平被认为可在精神分裂症患者中诱发强迫症（OCS）。然而，由于不管氯氮平如何治疗，OCS经常合并精神分裂症，因此氯氮平是否可以从头产生OCS尚不清楚。因此，在人类研究中，很难在氯氮平和OCS之间建立因果关系。为了解决这个问题，我们询问氯氮平的慢性治疗是否可以在小鼠中诱发强迫症（OCD）样行为。我们以60天的间隔给小鼠注射了连续4次用氯氮平包埋的长期连续释放药丸，然后监测小鼠直至40 wk的类似OCD的行为。年龄。我们发现氯氮平最早可在30周内增加美容行为。年龄。我们还研究了氯氮平对Sapap3基因敲除（KO）小鼠修饰行为的影响，这是OCD的著名动物模型。在Sapap3杂合型KO小鼠中，氯氮平比野生型小鼠更早地增加修饰行为，这表明氯氮平与OCD基因相互作用。氟西汀常用于OCS和OCD的治疗，可减轻氯氮平引起的疏导行为。这些数据表明，慢性氯氮平治疗可在小鼠中产生类似OCD的行为，并支持氯氮平不产生精神分裂症而从头产生OCS的假说。