Effects of Ethanol Exposure on Mesolimbic Dopamine

乙醇暴露对中脑边缘多巴胺的影响

• 批准号: 6825549
• 负责人: Evgeny Alexander BUDYGIN
• 金额: $ 7.18万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6825549
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; behavior test; biological signal transduction; blood tests; dopamine; electrodes; ethanol; extracellular; laboratory rat; neural transmission; nucleus accumbens; reinforcer

DESCRIPTION (provided by applicant): Ethanol is a widely abused, reinforcing drug. Researchers have long aimed to elucidate the mechanisms of ethanol action in the brain. Considerable advances have been made in identifying the neural substrates that mediate the reinforcing actions of ethanol. In fact, the hypothesis that dopamine (DA), and specifically elevated DA in the nucleus accumbens (Nac), is involved in ethanol reinforcement is widely accepted. However, many questions remain about the neurochemical consequences of these DA changes. The goal of the proposed study is to further investigate the influence of chronic ethanol on dopaminergic signaling in the brain using a new experimental tool. Fast-scan cyclic voltammetry, allowing extremely sensitive spatial and temporal measurements of extracellular DA, will be used to directly assess the consequences of chronic ethanol on DA release and uptake in the Nac of freely moving rats. We will test the hypothesis that chronic ethanol exposure leads to adaptations in dopaminergic transmission aimed at decreasing dopamine signaling. We expect that chronic ethanol exposure will induce a substantial suppression of DA release, leading to a compensatory decrease of DA uptake. In any case, the results of this study will provide valuable information on the modulation of dopaminergic neurotransmission by chronic ethanol.

描述（由申请人提供）：乙醇是一种广泛滥用的强化药物。长期以来，研究人员一直致力于阐明乙醇在大脑中的作用机制。在确定介导乙醇强化作用的神经底物方面已经取得了相当大的进展。事实上，多巴胺（DA），特别是中脑核（Nac）中升高的DA参与乙醇强化的假设被广泛接受。然而，关于这些DA变化的神经化学后果仍然存在许多问题。这项研究的目的是使用一种新的实验工具进一步研究慢性乙醇对大脑中多巴胺能信号传导的影响。快速扫描循环伏安法，允许非常敏感的空间和时间的测量细胞外DA，将被用来直接评估的后果，慢性乙醇对DA的释放和摄取的自由活动的大鼠的NAC。我们将检验这一假设，即慢性乙醇暴露导致多巴胺能传递的适应，旨在减少多巴胺信号。我们预计，慢性乙醇暴露将诱导大量抑制DA释放，导致DA摄取的代偿性减少。在任何情况下，这项研究的结果将提供有价值的信息调制多巴胺能神经传递的慢性乙醇。