Does maternal administration of antipsychotics have a prophylactic effect on the development of psychotic features in offspring?: An animal study using the asphyxia model of schizophrenia.

母亲服用抗精神病药物是否对后代精神病特征的发展有预防作用？：使用精神分裂症窒息模型的动物研究。

• 批准号: 22791118
• 负责人: TAKAHASHI Taro
• 金额: $ 2.58万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791118/
• 关键词: 精神薬理学; 非定型抗精神病薬; 統合失調症; 神経幹細胞; 仮死モデル; クロザピン; 早期介入

The asphyxia model of schizophrenia, in which rat pups were exposed to 15 min of intrauterine anoxia during Cesarean section birth, showed a reduction in hippocampal dentate granule cells at 6 weeks of age and dopaminergic dysregulation at 12 weeks after birth, both have been regarded as schizophrenia-like phenotypes. Using this model, we examined in this study whether administration of antipsychotics to mothers prevent the development of schizophrenia-like features in their offspring. Pregnant female rats were administered daily either with clozapine(0. 5 or 5. 0 mg/kg), haloperidol(0. 1 or 1. 0 mg/kg), or saline by intraperitoneal infusions. Their pups were delivered Cesarean section with or without asphyxia. Twelve weeks after birth, pups were challenged with methamphetamine(0. 5 or 2. 0 mg/kg) or saline, and their locomotor activity were measured. As a result, there were no significant effects of either dose of clozapine or haloperidol on methamphetamine-induced locomotor activity in those pups.These results failed to support the hypothesis that maternal administrations of antipsychotic might have a prophylactic effect on the development of psychotic features in their offspring.

在精神分裂症窒息模型中，剖宫产时暴露15分钟宫内缺氧的大鼠幼仔，在出生后6周龄海马齿状颗粒细胞减少，在出生后12周龄多巴胺能失调，两者都被认为是精神分裂症样表型。使用这个模型，我们在这项研究中检验了母亲服用抗精神病药物是否能防止其后代出现精神分裂症样特征。怀孕的雌性大鼠每天给予氯氮平(0。5或5。0 mg/kg)，氟哌啶醇(0。1或1。0 mg/kg)，或通过腹腔注射生理盐水。他们的幼崽在有或没有窒息的情况下进行剖宫产。出生12周后，幼犬被注射甲基苯丙胺(0。5个或2个。0 mg/kg)或生理盐水，并测量其运动活动。结果，氯氮平或氟哌啶醇对甲基苯丙胺诱导的幼鼠运动活动均无显著影响。这些结果不能支持母亲服用抗精神病药物可能对其后代精神病特征的发展有预防作用的假设。

项目成果

Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferation in rats: reversal by fluoxetine.

• DOI: 10.1371/journal.pone.0009260
• 发表时间: 2010-02-17
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Suzuki K;Okada K;Wakuda T;Shinmura C;Kameno Y;Iwata K;Takahashi T;Suda S;Matsuzaki H;Iwata Y;Hashimoto K;Mori N
• 通讯作者: Mori N