Electrophysiology of alcohol in extended amygdala

扩展杏仁核中酒精的电生理学

• 批准号: 6650914
• 负责人: GEORGE Robert SIGGINS
• 金额: $ 27.06万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650914
• 关键词: GABA receptor; NMDA receptors; alcoholic beverage consumption; alcoholism /alcohol abuse; amygdala; behavioral /social science research tag; cooperative study; corticotropin releasing factor; craving; drug /alcohol abstinence; drug withdrawal; electrophysiology; ethanol; gene targeting; genetically modified animals; glutamate receptor; hormone receptor; laboratory mouse; membrane potentials; nucleus accumbens; opioid receptor; receptor expression; synapses; video microscopy; voltage /patch clamp

DESCRIPTION (provided by applicant): We have pursued electrophysiological studies of the role of synaptic transmitters, neuropeptides and their receptors in alcohol effects, with the rationale that these elements are the most sensitive sites of ethanol action. This project is based on behavioral findings that the nucleus accumbens (Nace) and extended amygdala are key areas in the reinforcing properties of abused drugs, and that these properties also may involve several transmitters (e.g., GABA, glutamate) and neuropeptides (e.g., CRF and opioids). The amygdala has been implicated in motivated behaviors and anxiety states, and it is hypothesized that these same neuropharmacological systems within the extended amygdala mediate the increases in ethanol self-administration that occur during withdrawal from chronic ethanol. Therefore, we propose several sets of experiments: 1) To begin in vitro brain slice studies of acute and chronic ethanol effects on membrane and synaptic properties of central amygdala (CeA) neurons and NAcc neurons in the mouse for comparison to our rat data, and to prepare for studies of murine genetic models. 2) To determine the role of CRF receptors, whose expression may be responsible for excessive alcohol consumption, by examining extended amygdala network and cellular functioning in brain slices taken from mice with knockouts for brain CRF-I receptors. 3) To determine the role of opiate receptors that could be responsible for excessive alcohol consumption, by examining extended amygdala network and cellular functioning in brain slices taken from rnice with knockouts for brain mu opiate and, later, delta opiate receptors. These studies will use amygdala and NAce brain slices and involve standard intracellular (current- and voltage-clamp) and "patch-slice" whole-cell clamp methods. The infrared DIC-videoniieroseopic method will be used to identify morphologically different cells types for comparison to electrophysiological and pharmacological properties. We will record evoked, pharmacologically-isolated monosynaptic currents or potentials, and spontaneous and miniature synaptic events, to test the specificity and site of action of ethanol effects. These studies should provide important new information on possible sequelac of ethanol intoxication at the cellular level, and, by comparisons of ethanol and peptide actions in control, ethanol-withdrawn, protracted abstinence, and knockout models, will also provide clues as to the cellular and ion channel correlates of ethanol dependence.

描述（由申请人提供）： 我们对突触的作用进行了电生理学研究， 递质、神经肽及其受体在酒精效应中的作用， 这些元素是乙醇作用的最敏感位点。 该项目是基于行为的研究结果，即核神经元（Nace） 和杏仁核的延伸是增强受虐者的能力的关键区域 药物，并且这些性质还可能涉及几种发射器（例如， GABA、谷氨酸）和神经肽（例如，CRF和阿片类药物）。杏仁核有 与动机行为和焦虑状态有关， 假设这些相同的神经药理学系统在扩展的 杏仁核介导乙醇自我给药的增加， 从慢性酒精中戒断因此，我们提出了几套 实验：1）开始急性和慢性脑缺血的体外脑切片研究 乙醇对中央杏仁核（CeA）膜和突触特性的影响 神经元和NAcc神经元的小鼠进行比较，我们的大鼠数据，并 为小鼠遗传模型的研究做准备。2)确定通用报告格式的作用 受体，其表达可能导致过量酒精 消耗，通过检查扩展杏仁核网络和细胞功能 在脑CRF-I受体敲除小鼠的脑切片中。第三章 为了确定阿片受体的作用， 过量饮酒，通过检查扩展的杏仁核网络， 从敲除脑的rnice中取出的脑切片中的细胞功能 μ阿片受体和δ阿片受体。这些研究将使用杏仁核 和NAce脑切片，并涉及标准的细胞内（电流和 电压钳）和“膜片”全细胞钳方法。红外 将采用DIC-视频显微镜方法进行形态学鉴定 不同的细胞类型，用于与电生理和 药理学特性我们将记录诱发的，药理分离的 单突触电流或电位，以及自发和微型突触 事件，以测试乙醇效应的特异性和作用部位。这些 研究应提供重要的新信息， 乙醇中毒在细胞水平，并通过比较乙醇和 肽的作用，控制，乙醇撤出，延长禁欲，和 敲除模型也将为细胞和离子通道提供线索 酒精依赖的相关因素。