微清蛋白中间神经元在氯胺酮致大鼠精神分裂样表现中的作用

Role of parvalbumin interneurons in ketamine-induced psychosis-like responses in rats

目的微清蛋白(parvalbumin,PV)中间神经元功能失调可能与多种精神疾患发病相关,文中探讨PV中间神经元在氯胺酮致大鼠精神分裂样表现中的作用。方法 36只Wistar雄性大鼠随机均分为3组:等渗盐水组(S组)、氯胺酮5 mg/kg组(K1组)、氯胺酮30 mg/kg组(K2组);连续用药5 d,1次/d。最后1次给药后30 min及60 min,通过敞箱实验观察大鼠自主活动,并记录给药后60 min内的刻板行为评分。行为学实验结束后,取大鼠前额皮层,检测PV中间神经元的改变。结果与S组比较,K2组大鼠给药后30 min及60 min自主活动均明显增强,刻板行为评分显著增高,符合精神分裂症大鼠表现,PV阳性中间神经元数量显著减少(P<0.05)。K1组大鼠仅在给药后30 min出现自主活动增强(P<0.05),其他指标则无显著变化(P>0.05)。结论氯胺酮致精神分裂样表现可能与PV阳性中间神经元数量减少有关。

Objective The dysfunction of parvalbumin （PV） interneurons may contribute to the pathogenesis of various psychiatric disorders. This study was to explore the effect of PV interneurons in ketamine-indueed psychosis-like responses in rats. Methods Thirty-six male Wistar rats were equally randomized into three groups ： saline （ S）, ketamine 5 mg/kg （ K1 ）, and ketamine 30 mg/kg （ K2）, and medicated qd for 5 days continuously. Locomotor activities were observed at 30 and 60 rain after the last administration by open field test, and the scores of stereotyped behavior within 60 min were recorded. Immunohistochemistry was employed to detect the change of PV positive interneurons in the prefrontal cortex immediately after ethologic measurement. Results Compared with the S group, the K2 group showed significantly increased locomotor activities and scores of stereotyped behavior at both 30 and 60 min after medication, which were consistent with the psychotic performance of schizophrenia rats, but remarkably reduced numbers of PV-positive interneurons （ P 〈 0.05 ）, while the K1 group exhibited enhanced locomotor activities only at 30 rain （ P 〈 0.05 ）, with no other statistically significant differences （ P 〉 0.05 ）. Conclusion The reduction of PV-positive interneurons may play an important role in ketamine-induced psychosis-like responses in rats.