Ethanol effects on GABA-serotonin interactions in the Dorsal Raphe Nucleus

描述（由申请人提供）：酒精依赖是一种缺乏有效治疗的严重疾病。5 -羟色胺系统的失调被广泛认为与酒精依赖有关，尽管人们对慢性乙醇对5 -羟色胺神经元本身或它们所属的微回路的影响知之甚少。在中脑背缝（DR）中，5 -羟色胺神经元的活动由局部GABA神经元调节。慢性乙醇对DR的GABA神经元及其对血清素神经元活动的调节的影响迄今尚未被探索。利用全细胞切片电生理学、慢性乙醇蒸汽暴露、行为学、光遗传学和化学遗传学方法，本研究的目标是验证慢性乙醇诱导DR内GABA神经元功能的适应，从而改变血清素神经元活动的调节的假设。这些实验的结果将提供DR GABA神经元在慢性乙醇暴露导致的血清素活性失调中的作用，并将为针对血清素系统治疗酒精中毒的药物疗法的发展提供信息。

DESCRIPTION (provided by applicant): Alcohol dependence is a serious disorder for which effective treatments are lacking. Dysregulation of the serotonin system has been widely implicated in alcohol dependence though little is known about chronic ethanol's effects on serotonin neurons themselves or the microcircuit to which they belong. In the dorsal raphe (DR), a midbrain structure from which 50% of the brain's serotonin arises, serotonin neuron activity is modulated by local GABA neurons. The effects of chronic ethanol on GABA neurons of the DR and their modulation of serotonin neuron activity have not been explored to date. Using whole-cell slice electrophysiology, chronic ethanol vapor exposure, behavioral, optogenetic and chemogenetic approaches, the goal of this proposal is to test the hypothesis that chronic ethanol induces adaptations in GABA neuron function within the DR, resulting in altered modulation of serotonin neuron activity. The results of the proposed experiments will provide insight into the role of DR GABA neurons in dysregulated serotonin activity resulting from chronic ethanol exposure and will inform the development of pharmacotherapies targeting the serotonin system for the treatment of alcoholism.