Oxytocin effects on GABAergic signaling in the alcohol dependent CeA.

项目总结/摘要 酒精中毒是一种慢性疾病，表现为强迫性寻求和消费酒精， 从娱乐性饮酒到滥用和依赖的转变。酒精依赖和戒断是 其特征在于由被招募的大脑压力系统引起的负面情绪状态。杏仁核 核团，特别是中央杏仁核（CeA），被认为是负面情绪回路的枢纽， 在这个大脑结构中，促应激和抗应激神经肽的作用对于酒精的形成至关重要 依赖CeA主要含有GABA能神经元，抑制性突触对GABA能神经元非常敏感。 急性乙醇，并在急性和慢性乙醇消耗的行为效应中发挥关键作用。亲- 已经发现应激神经肽如促肾上腺皮质激素释放因子（CRF）增强GABA能 而抗应激神经肽如孤啡肽/孤啡肽（N/OFQ）和孤啡肽/孤啡肽（N/OFQ）在脑内的传递中起重要作用。 神经肽Y（NPY）减少GABA能传递。抗压力信号和促压力信号之间的平衡 在向酒精依赖过渡期间受到干扰，其特征在于CRF系统过度活跃。 重要的是，一种抗应激神经肽，催产素（OT），已被证明可以减少饮酒， 给人类酗酒者服用时会出现戒断症状然而，没有研究调查了 OT及其与乙醇的相互作用对CeA中GABA能系统的影响。因此，这一目标 一个建议是表征OT对CeA GABA能信号传导的影响，其与急性乙醇的相互作用， 以及OT系统中乙醇依赖诱导的潜在神经适应，使用 电生理技术。该项目产生的数据将阐明 OT在CeA中，并提供重要的信息，神经元的变化，有助于过渡到 娱乐性饮酒会导致酒精依赖，并可能导致更好的发展 酒精中毒的治疗方法。

PROJECT SUMMARY/ABSTRACT Alcoholism is a chronic disorder described by compulsive seeking and consumption of alcohol, the result of a transition from recreational alcohol use to abuse and dependence. Alcohol dependence and withdrawal are characterized by negative emotional states resulting from recruited brain stress systems. The amygdalar nuclei, in particular the central amygdala (CeA), are considered a hub for negative emotional circuitry, and the role of pro- and anti-stress neuropeptides in this brain structure is critical for the development of alcohol dependence. The CeA contains primarily GABAergic neurons, and the inhibitory synapses are very sensitive to acute ethanol and play a critical role in the behavioral effects of acute and chronic ethanol consumption. Pro- stress neuropeptides like corticotropin releasing factor (CRF) have been found to enhance GABAergic transmission in the CeA, while anti-stress neuropeptides like nociceptin/orphanin FQ (N/OFQ) and neuropeptide Y (NPY) decrease GABAergic transmission. The balance between anti- and pro-stress signaling is perturbed during the transition to alcohol dependence, characterized by an overactive CRF system. Importantly, one anti-stress neuropeptide, oxytocin (OT), has been shown to decrease drinking and block withdrawal symptoms when administered to human alcoholics. However, no studies have investigated the effects of OT and its interactions with ethanol on the GABAergic system in the CeA. Therefore, the goal of this proposal is to characterize the effects of OT on CeA GABAergic signaling, its interactions with acute ethanol and the potential neuroadaptations induced by ethanol dependence in the OT system, using electrophysiological techniques. The data generated by this project will elucidate the mechanisms of action of OT in the CeA and provide important information to the neuronal changes that contribute to the transition from recreational alcohol consumption to alcohol dependence, and could lead to the development of better therapeutics in the treatment of alcoholism.