Electrophysiology of alcohol in extended amygdala

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最敏感的部位的理论基础。 这个项目是基于伏隔核(NACE)的行为学研究结果。 和延伸的杏仁核是滥用的强化特性的关键区域 药物，并且这些性质还可能涉及几个传递体(例如， GABA、谷氨酸)和神经肽(如CRF和阿片类物质)。杏仁核有 与动机行为和焦虑状态有牵连，而且 假设这些相同的神经药理系统在扩展 杏仁核调节乙醇自我给药的增加 在戒除慢性乙醇期间。因此，我们提出了几套 实验：1)开展急、慢性脑片的体外研究 乙醇对中央杏仁核(CEA)膜和突触特性的影响 小鼠的神经元和NAcc神经元与我们的大鼠数据进行比较，并 为研究小鼠遗传模型做准备。2)确定CRF的作用 受体，其表达可能与过量酒精有关 消费，通过检查扩展的杏仁核网络和细胞功能 取自大脑CRF-I受体基因敲除的小鼠的脑片。3) 为了确定阿片受体的作用可能负责 过量饮酒，通过检查扩展的杏仁核网络和 RNICE脑片中细胞功能的研究 MU阿片受体，后来是德尔塔阿片受体。这些研究将使用杏仁核 和NACE脑片，并涉及标准细胞内(电流-和 电压钳)和“膜片”全细胞钳制方法。红外线 将采用DIC-视频视觉法进行形态鉴定 不同类型的细胞与电生理和 药理特性。我们将记录被唤起的、药理隔离的 单突触电流或电位、自发突触和微型突触 事件，以测试酒精效应的特异性和作用部位。这些 研究应该为可能的后遗症提供重要的新信息 在细胞水平上的乙醇中毒，通过比较乙醇和 多肽在控制、酒精戒断、长期戒断和 基因敲除模型，也将提供关于细胞和离子通道的线索 酒精依赖的相关因素。

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.