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.

我们以前的研究表明，产前酒精暴露产生 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 通过DA激动剂给药进行正常化。中脑DA神经传递 参与许多重要的中枢神经系统功能，包括奖赏、运动 控制注意力和自发活动。因此，产前乙醇 手术引起的多巴胺功能减退可能有助于 注意力/多动问题通常在患有 胎儿酒精综合征（FAE/FAS）拟议 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通过以下方式使这些变化正常化： 多巴胺激动剂我们还将启动行为实验， 与多巴胺功能减退和注意力问题有关此外该 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。的结果 这些研究将使我们更好地了解 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。