INIA Stress and Chronic Alcohol Interactions: CORE2: Stress-CIE Drinking Mouse Core

项目摘要 虽然压力对乙醇消耗的影响已经在几种动物模型中进行了广泛的研究， 这些研究通常得出模棱两可的结果，其结果取决于许多因素 包括使用的应激源的类型、应激呈现的时间和初始乙醇偏好。期间 在当前的资助期内，本核心项目的工作重点是研究压力与 在依赖模型中饮酒，涉及慢性间歇性乙醇（CIE）暴露的重复循环。 研究表明，在使用乙醇之前， 饮酒会议产生了显着增加乙醇饮用CIE暴露的小鼠，但没有改变 乙醇摄入量的非依赖性小鼠。这种可靠和强大的FSS诱导的选择性增强饮水 在依赖性小鼠中，血液乙醇水平增加了近3倍。有趣的是，其他压力 程序（例如，约束，脚电击，社会失败）并没有产生这种效果，这表明FSS相互作用 与CIE曝光以独特的方式，以促进进一步增加乙醇饮用。因此，该CIE-FSS 饮酒模型非常适合评估潜在的药物，不仅可以减少过量的 依赖性相关的饮酒，而且还脾气的能力，进一步加强这种升高的饮酒。 因此，这款Stress-CIE Drinking Mouse Core的主要功能是利用CIE-FSS Drinking模型 作为一个行为平台，以评估药物对男性和女性依赖者乙醇消耗量的影响 和非依赖性小鼠。选择用于评价的药物是基于其据称的靶向抗- 压力和神经炎症过程涉及过量饮酒，从而使 核心提供服务的研究项目的翻译目标在INIAstress和 神经免疫联合体。Core的另一个功能是将脑组织样本分发给INIA 研究人员，以促进更全面的基因组和神经研究有关的模型。这个， 反过来，这将有助于发现新的潜在新靶点和治疗策略， 这个核心。综上所述，Stress-CIE饮用小鼠核心的拟议研究计划将提供 为INIAstress和INIAneuroimmune Consortia以及一般酒精研究提供宝贵服务 领域Stress-CIE饮水小鼠核心的总体目标是促进和帮助识别和 开发新的治疗方法，减少与压力有关的过度饮酒，更广泛地说， 酒精使用障碍

PROJECT SUMMARY While the effect of stress on ethanol consumption has been extensively studied in several animal models, these studies have generally yielded equivocal findings, with results dependent on a number of factors including the type of stressor used, timing of stress presentation, and initial ethanol preference. During the current funding period, work conducted in this Core has focused on examining the interaction of stress with drinking in a model of dependence that involves repeated cycles of chronic intermittent ethanol (CIE) exposure. Studies demonstrated that repeated brief forced swim stress (FSS) exposure administered prior to ethanol drinking sessions produced a significant increase in ethanol drinking in CIE-exposed mice, but did not alter ethanol intake in nondependent mice. This reliable and robust FSS-induced selective enhancement of drinking in dependent mice produced a nearly 3-fold increase in blood ethanol levels. Interestingly, other stress procedures (e.g., restraint, foot-shock, social defeat) did not produce this effect, suggesting that FSS interacts with CIE exposure in a unique manner to promote further increases in ethanol drinking. Thus, this CIE-FSS drinking model is ideally suited to evaluate potential medications that may not only reduce excessive dependence-related drinking, but also temper the ability of stress to further enhance this elevated drinking. Accordingly, a major function of this Stress-CIE Drinking Mouse Core is to utilize the CIE-FSS Drinking model as a behavioral platform to evaluate medication effects on ethanol consumption in male and female dependent and nondependent mice. Medications selected for evaluation are based on their purported ability to target anti- stress and neuroinflammatory processes implicated in excessive alcohol consumption, thereby enabling the Core to provide service to the translational objectives of research projects in the INIAstress and INIAneuroimmune Consortia. Another function of the Core is to distribute brain tissue samples to INIA investigators to facilitate more comprehensive genomic and neural investigations in relation to the model. This, in turn, will facilitate new discoveries of potential novel targets and treatment strategies that can be tested in this Core. Taken together, the proposed research plan for the Stress-CIE Drinking Mouse Core will provide valuable service to the INIAstress and INIAneuroimmune Consortia, as well as the general alcohol research field. The overall goal of the Stress-CIE Drinking Mouse Core is to facilitate and aid in the identification and development of new treatment approaches for reducing stress-related excessive drinking and, more broadly, alcohol use disorders.