Characterizing the Edinger-Westphal response to alcohol

这项提议的总体目标是描述Edinger-Westphal核(EW)对酒精的反应。我们的实验室和其他实验室已经表明，EW通过各种给药途径对酒精产生强烈的反应。由于EW是酒精给药的一个重要靶点，拟议的研究旨在阐明其在酒精中毒中的机制和作用。本研究的具体目的是：1)研究酒精对EW反应的神经化学特征；2)确定酒精诱导EW细胞激活的候选神经递质受体；3)确定EW显微注射受体拮抗剂阻断EW激活的行为效应。神经化学将使用免疫组织化学和原位技术进行分析。受体的识别将包括各种受体拮抗剂的全身给药和随后通过c-Fos的免疫组织化学分析EW的激活。将使用几种常见的行为分析(即酒精敏感性测量、运动活动和焦虑测量)来评估饮酒后EW神经活动的作用。假设EW的激活针对由特定受体亚型激活的特定神经元子集。它进一步假设，这些神经元的激活参与了酒精诱导的行为效应的产生。这一建议的发现将对理解EW激活的机制作用及其参与与醉酒相关的行为具有重要意义。此外，这项研究将有助于寻求酒精中毒的药物治疗方法。

The overall goal of this proposal is to characterize the response of the Edinger-Westphal nucleus (EW) to alcohol. It has been shown in our lab and others that EW is robustly responsive to alcohol by various routes of administration. Because EW is a prominent target for alcohol administration, the proposed studies are intended to elucidate its mechanism and role in alcohol intoxication. The specific aims of this proposal are: 1) to characterize the neurochemistry of EW response to alcohol administration, 2) to identify candidate neurotransmitter receptors mediating activation of EW cells following alcohol administration, and 3) to identify behavioral effects of EW microinjected receptor antagonists blocking activation of EW. Neurochemistry will be analyzed using immunohistochemical and in situ techniques. Identification of receptors will involve the systemic administration of various receptor antagonists and subsequent analysis of EW activation by immunohistochemical analysis of c-Fos. Several common behavioral assays (i.e. alcohol sensitivity measures, locomotor activity, and anxiety measures) will be used to assess the role of EW neural activity following alcohol administration. It is hypothesized that activation of EW is targeted to a specific subset of neurons that are activated by specific receptor subtypes. It is further hypothesized that activation of these neurons is involved in the generation of alcohol-induced behavioral effects. The findings of this proposal will be important in understanding the mechanistic role of EW activation and its involvement in behaviors associated with intoxication. Furthermore, this investigation will aid in the pursuit of pharmacological treatments for alcoholism.