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

项目总结 虽然压力对酒精消耗的影响已经在几个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，结果取决于许多因素 包括使用的压力源的类型，压力呈现的时间，以及最初的酒精偏好。在.期间 在目前的资助期内，在该核心开展的工作重点是研究压力与 在一种依赖模型中饮酒，这涉及到慢性间歇性乙醇(CIE)暴露的重复循环。 研究表明，反复短暂的强迫游泳应激(FSS)暴露在酒精之前 饮酒使暴露于CIE的小鼠的酒精饮用量显著增加，但没有改变 非依赖小鼠的酒精摄入量。这种可靠和健壮的FSS诱导的选择性饮酒增加 在依赖的小鼠中，血液中的乙醇水平几乎增加了3倍。有趣的是，其他压力 程序(例如，束缚、脚部电击、社交失败)没有产生这种效果，这表明FSS相互作用 以一种独特的方式与CIE接触，促进酒精饮用量的进一步增加。因此，该CIE-FSS 饮酒模型非常适合于评估潜在的药物，这些药物不仅可以减少过量 与饮酒相关的依赖，也会缓和压力的能力，从而进一步提升饮酒的水平。 因此，该压力-CIE饮酒鼠标核心的主要功能是利用CIE-FSS饮酒模型 作为评估药物对男性和女性依赖者酒精消费影响的行为平台 和不依赖的小鼠。选择进行评估的药物是基于其声称的靶向抗逆转录病毒的能力 压力和神经炎症过程与过量饮酒有关，从而使 为INIAStress和INIAStress的研究项目的翻译目标提供服务 神经免疫联盟。Core的另一个功能是将脑组织样本分发给INIA 研究人员为与该模型有关的更全面的基因组和神经研究提供便利。这, 反过来，将促进潜在的新靶点和治疗策略的新发现，可以在 这个核心。综上所述，针对应激-CIE饮酒鼠核心的拟议研究计划将提供 对INIA应激和INIA神经免疫联盟以及普通酒精研究有价值的服务 菲尔德。压力-CIE饮酒鼠标核心的总体目标是促进和帮助识别和帮助 开发新的治疗方法以减少与压力相关的过度饮酒，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.