DOPAMINE FUNCTION AFTER PRENATAL ETHANOL EXPOSURE

产前乙醇暴露后的多巴胺功能

• 批准号: 6371588
• 负责人: ROH-YU SHEN
• 金额: $ 22.74万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6371588
• 关键词: attention; behavior test; developmental neurobiology; dopamine; dopamine agonists; dopamine receptor; electrophysiology; embryo /fetus drug adverse effect; ethanol; fetal alcohol syndrome; laboratory rat; neurons; neuropharmacology; receptor sensitivity

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.

我们先前的研究表明，产前乙醇暴露会产生 中脑多巴胺的电活动持续减少 神经元和改变多巴胺受体的敏感性。这些变化是 由DA激动剂给药归一化。中脑DA神经传递 参与了许多重要的CNS功能，包括奖励，电动机 控制注意力和运动活动。因此，产前乙醇 暴露诱导的多巴胺功能功能不全可能有助于 患有儿童通常观察到的注意力/多动症问题 胎儿酒精效应，胎儿酒精综合征（FAE/FAS）。在提议中 研究，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 产前的多巴胺系统的产后发育过程 乙醇暴露。我们将研究如何通过 多巴胺激动剂。我们还将启动行为实验 相关的多巴胺功能障碍和注意力问题。另外， 细胞导致多巴胺的电活动减少 将检查产前乙醇暴露后的神经元。结果 这些研究将使我们在病因学的理解中更好地理解 FAE/FAS中的行为症状，并帮助我们开发更合适的 动物模型可以推进FAE/FAS的药理治疗。