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

乙醇对中缝背核 GABA-血清素相互作用的影响

• 批准号: 8783666
• 负责人: EMILY Geyer LOWERY-GIONTA
• 金额: $ 5.56万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-06 至 2016-05-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8783666
• 关键词: Acute; Alcohol dependence; Alcohols; Attenuated; Behavioral; Brain; Calcium; Cell Nucleus; Cells; Chronic; Clinical; Coupled; Data; Development; Disease; Dorsal; Electrophysiology (science); Ethanol; Functional disorder; Goals; Health; Lesion; Mediating; Methods; Midbrain structure; Mus; Neurons; Outcome; Pathology; Pharmacotherapy; Population; Pre-Clinical Model; Relapse; Reporter; Role; Serotonin; Slice; Stress; Swimming; Synapses; System; Testing; alcohol effect; alcohol exposure; alcohol use disorder; alcoholism therapy; calcium indicator; chronic alcohol ingestion; dorsal raphe nucleus; drinking; effective therapy; gamma-Aminobutyric Acid; insight; mouse model; neuroadaptation; optogenetics; postsynaptic; public health relevance; receptor; research study; stem; therapeutic development; transmission process; vapor

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.

描述（由申请人提供）：酒精依赖是一种严重的疾病，缺乏有效的治疗方法。血清素系统的失调与酒精依赖有广泛的关联，尽管人们对长期乙醇对血清素神经元本身或它们所属的微电路的影响知之甚少。在中缝背侧 (DR) 中，大脑中 50% 的血清素由中脑结构产生，血清素神经元的活动由局部 GABA 神经元调节。迄今为止，尚未探索长期乙醇对 DR 的 GABA 神经元的影响及其对血清素神经元活性的调节。使用全细胞切片电生理学、慢性乙醇蒸气暴露、行为、光遗传学和化学遗传学方法，该提案的目的是测试以下假设：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。拟议实验的结果将深入了解 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，并将为开发针对治疗酒精中毒的血清素系统的药物疗法提供信息。