Preventive effects of 5-HT agonists on the abnormal development of of 5-HTergic system induced by prenatal ethanol exposure in rats

我们给药5-HT 1A激动剂，伊沙匹隆，或5-HT 2A/2C激动剂，DOI，对产前乙醇（EtOH）暴露的大鼠在E13-20。基于我们对E20的电化学观察，两种激动剂的给药防止了E10-20期间EtOH暴露诱导的中脑中缝核中5-HT能神经元数量的减少。 Ipsapirone还减轻了异常的焦虑样行为中看到的高架十字迷宫测试所造成的产前EtOH暴露。胎脑中基因表达的定量分析显示，Phox 2b的表达，这是与5-HT神经元的发育，减少产前暴露后EtOH，但DOI减弱EtOH对Phox 2b基因表达的影响。我们的结论是，产前EtOH暴露对5-HT神经元的发育和行为变化的影响，导致改变5-HTergic系统可以减轻通过5-HT 1A或5-HT 2A/2C受体在E13-20期间的信号增强。

We administered the 5-HT1A agonist, ipsapirone, or the 5-HT2A/2C agonist, DOI, against prenatal ethanol (EtOH)-exposed rats during E13-20. Based on our immunohistochamical observation on E20, administrations of both agonists prevented a reduction in the number of 5-HTergic neurons in the midbrain raphe nuclei induced by EtOH exposure during E10-20. Ipsapirone also alleviated an abnormality of anxiety-like behavior seen in an elevated-plus maze test caused by prenatal EtOH exposure. The quantitative analysis of gene expression in fetal brains revealed that an expression of Phox2b, which is related to development of 5-HT neurons, was reduced after prenatal exposure to EtOH, but DOI attenuated the effect of EtOH on Phox2b gene expression. We concluded that the effect of prenatal EtOH exposure on development of 5-HT neurons and behavioral changes resulting in the altered 5-HTergic systems could be alleviated by the enhancement of signaling via 5-HT1A or 5-HT2A/2C receptors during E13-20.