DOPAMINE FUNCTION AFTER PRENATAL ETHANOL EXPOSURE

产前乙醇暴露后的多巴胺功能

• 批准号: 6198578
• 负责人: ROH-YU SHEN
• 金额: $ 19.55万
• 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/6198578
• 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.

我们之前的研究表明，产前接触乙醇会产生 中脑多巴胺电活动持续减少 神经元并改变多巴胺受体的敏感性。这些变化是 通过 DA 激动剂给药使其正常化。中脑 DA 神经传递 参与许多重要的中枢神经系统功能，包括奖励、运动 控制注意力和运动活动。因此，产前乙醇 暴露引起的多巴胺功能减退可能会导致 患有以下疾病的儿童中常见的注意力/多动问题 胎儿酒精效应，胎儿酒精综合症（FAE/FAS）。在提议的 研究中，我们将使用细胞外和细胞内 电生理记录技术进一步表征 产前多巴胺系统的产后发育过程 乙醇暴露。我们将研究如何使这些变化正常化 多巴胺激动剂。我们还将启动行为实验 将多巴胺功能减退和注意力问题联系起来。此外， 细胞导致多巴胺电活动减少 将检查产前乙醇暴露后的神经元。结果 这些研究将加深我们对病因的理解 FAE/FAS 中的行为症状并帮助我们制定更合适的 动物模型以推进 FAE/FAS 的药物治疗。