DOPAMINE FUNCTION AFTER PRENATAL ETHANOL EXPOSURE

我们之前的研究表明，产前接触酒精会产生 中脑多巴胺的电活动持续减少 并改变多巴胺受体的敏感性。这些变化是 用DA激动剂治疗后恢复正常。中脑DA神经传递 参与了许多重要的中枢神经系统功能，包括奖赏、运动 控制注意力，控制活动。因此，产前酒精 暴露诱导的多巴胺功能低下可能导致 注意/多动问题通常观察到的儿童 胎儿酒精效应，胎儿酒精综合征(FAE/Fas)。在建议的 研究中，我们将使用细胞外和细胞内 电生理记录技术以进一步表征 出生前多巴胺系统的出生后发育过程 酒精暴露。我们将研究如何将这些变化正常化 多巴胺激动剂。我们还将启动行为实验，以 与多巴胺功能减退和注意力问题相关。此外， 导致多巴胺电活动减少的细胞 胎儿期酒精暴露后的神经元将被检查。结果是 这些研究将加深我们对本病病因的理解。 FAE/Fas中的行为症状并帮助我们发展出更合适的 促进FAE/Fas药物治疗的动物模型

Our previous studies demonstrate that prenatal ethanol exposure produces a persistent reduction in the electrical activity of midbrain dopamine neurons and alters dopamine receptor sensitivity. These changes are normalized by DA agonist administration. Midbrain DA neurotransmission is involved in many important CNS functions including reward, motor control attention, and locomotor activity. Therefore, prenatal ethanol exposure-induced dopamine hypofunction may contribute to the attention/hyperactivity problems commonly observed in children with fetal alcohol effects, fetal alcohol syndrome (FAE/FAS). In the proposed studies, we will use extracellular and intracellular electrophysiological recording techniques to further characterize the postnatal developmental process of dopamine systems that prenatal ethanol exposure. We will study how these changes may be normalized by dopamine agonists. We will also initiate behavioral experiments to correlate dopamine hypofunction and attention problems. In addition, the cellular leading to a reduction in the electrical activity of dopamine neurons after prenatal ethanol exposure will be examined. The results of these studies will better our understanding in the etiology of behavioral symptoms in FAE/FAS and help us to develop more appropriate animal models to advance the pharmacological treatment of FAE/FAS.