Effects of Ethanol Exposure on Mesolimbic Dopamine

描述(申请人提供)：乙醇是一种被广泛滥用的强化药物。长期以来，研究人员一直致力于阐明酒精在大脑中的作用机制。在识别调节乙醇增强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)，特别是伏隔核(NAC)中DA的升高，与乙醇强化有关的假设被广泛接受。然而，关于这些DA变化的神经化学后果仍然存在许多问题。这项拟议的研究的目标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的影响。快速扫描循环伏安法允许对细胞外DA进行极其灵敏的空间和时间测量，将被用于直接评估慢性乙醇对自由活动大鼠NAC中DA释放和摄取的影响。我们将测试这一假设，即长期酒精暴露会导致多巴胺能传递的适应，目的是减少多巴胺信号。我们预计慢性酒精暴露将导致DA释放的显著抑制，导致DA摄取的代偿性下降。无论如何，本研究的结果将为慢性乙醇对多巴胺能神经传递的调节提供有价值的信息。

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.