This research program is designed to investigate epigenetic influences of the neurotransmitter serotonin (5-HT) on cell proliferation, neruite outgrowth, and gene expression in developing rat brain, using a variety of experimental approaches. These studies are based on the hypothesis that 5-HT. contained in growing axons, regulates the proliferation and/or differentiation of target cells (neuroepithelial cells, neurons or glia) with which these axons come into contact during critical periods of development. Specifically, we will investigate the effects of 5-HT and related drugs on 1) cell proliferation in the ventricular zone (neuroepithelium) of the embryonic rat brain; 2) proliferation of cultured neuro-epithelial cells, embryonic gila, and postnatal astrocytes: 3) neurite outgrowth by cultured 5-HT neurons and their catecholaminergic targets (dopaminergic substantia nigra and brainstem noradrenergic groups), and 4) gene expression by developing catecholamine neurons, embryonic gila and postnatal astrocytes. We will also investigate the possible mediation of these effects by 5-HT receptors and uptake mechanisms. The results of these studies may be important for understanding the etiology of abnormal brain function in offspring of mothers who use or abuse psychoactive drugs during pregnancy. particularly those substances which act through serotonergic mechanisms.
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