The Role of GABA Co-release from Dopamine Neurons in Ethanol Consumption

项目摘要 酒精使用障碍是一个严重的公共卫生问题，但其原因仍然难以捉摸;我们仍然不完全了解。 了解驱动EtOH消耗的神经生理机制。所有成瘾药物都会激活 多巴胺（DA）神经元，这被认为只会导致神经递质的突触增加 DA.然而，最近的证据表明，DA神经元也释放抑制性神经递质 GABA，它使DA神经元对纹状体具有另一种控制水平。使用转基因小鼠， 病毒操纵，和乙醇饮用行为，这里提出的实验将提供一个 机械帐户的作用，GABA共释放DA神经元在乙醇消耗。结果 还将提供另一个层次的机制-使用双光子成像，光遗传学， 电生理学，DA和GABA共同释放对树突兴奋性的突触后后果 将被定义。从这些研究中获得的机制见解可以为新型治疗策略提供信息 酒精使用障碍

PROJECT SUMMARY Alcohol use disorder is a serious public health concern, yet its cause remains elusive; we still do not fully understand the neurophysiological mechanisms that drive EtOH consumption. All addictive drugs activate dopamine (DA) neurons, and this was assumed to only cause a synaptic increase of the neurotransmitter DA. However, recent evidence suggests that DA neurons also release the inhibitory neurotransmitter GABA, which equips DA neurons with another level of control over the striatum. Using transgenic mice, viral manipulations, and EtOH drinking behavior, the experiments proposed here will provide a mechanistic account of the role of GABA co-release from DA neurons in EtOH consumption. The results will also provide another level of mechanism – using two-photon imaging, optogenetics, and electrophysiology, the post-synaptic consequences of DA and GABA co-release on dendritic excitability will be defined. The mechanistic insight gained from these studies could inform novel treatment strategies for alcohol use disorder.