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

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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.