Mouse Chronic Intermittent Ethanol (CIE) Core

小鼠慢性间歇性乙醇 (CIE) 核心

• 批准号: 8424255
• 负责人: Marcelo F. Lopez
• 金额: $ 36.92万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-10 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8424255
• 关键词: Acute; Address; Adrenal Glands; Alcohol abuse; Alcohol consumption; Alcohol withdrawal syndrome; Alcoholism; Animal Model; Animals; Automobile Driving; Behavioral; Brain; C57BL/6 Mouse; Chronic; Chronic stress; Collection; Data; Dependence; Development; Endocrine; Ensure; Ethanol; Ethanol dependence; Evaluation; Exposure to; Fostering; Gene Deletion; Gene Targeting; Genetic; Genomics; Genotype; Goals; Heavy Drinking; Homeostasis; Knockout Mice; Laboratories; Literature; Mediating; Modeling; Molecular; Mus; Organ; Organism; Outcome Study; Physiological; Plasma; Play; Procedures; Public Health; Regulation; Reliability of Results; Research; Research Personnel; Research Project Grants; Resources; Rewards; Role; Standardization; Stress; System; Taxes; Tissue Sample; alcohol exposure; allostasis; data integration; drinking; drinking behavior; effective therapy; experience; mouse model; neuroadaptation; neurochemistry; neurophysiology; novel; preference; prevent; relating to nervous system; stressor; time use

DESCRIPTION (provided by applicant): While the effect of stress on ethanol consumption has been extensively studied in several animal models, these studies have yielded equivocal findings, with results depending on a myriad of factors including the type of stressor used, timing of stress presentation, initial ethanol preference, among many others. The INIAstress Consortium has contributed to this literature, mostly demonstrating that acute/sub-chronic administration of various stressors results in suppression of ethanol intake in various mouse models. In contrast, results from our laboratory have demonstrated that repeated cycles of chronic intermittent ethanol (CIE) exposure reliably produces escalation of voluntary ethanol drinking in C57BL/6J mice. Further, it has become evident that repeated cycles of CIE exposure constitutes a potent stressor itself, producing profound disturbances in neural and physiological systems. This has led to the overarching notion that chronic ethanol exposure and withdrawal experience produces persistent perturbations in neurophysiological systems within stress and reward circuits that tax the organism beyond normal homeostatic limits (i.e., a state of allostasis). These neuroadaptations are postulated to not only impact stress responsiveness, but also play a role in driving/promoting excessive levels of drinking associated with dependence. A major objective of this Mouse CIE Core is to provide comprehensive behavioral phenotypic evaluation of the effect of ethanol dependence (CIE exposure) and stress on voluntary ethanol intake in various genetic mouse models, as well as provide organ tissue samples (e.g., brain, plasma, adrenals) for use in other INIAstress projects. Specifically, studies conducted in this Core will focus on characterizing the effects of CIE exposure alone and in combination with various stress procedures on voluntary drinking in dependent and nondependent animals. These studies will be conducted with C57BL/6 mice, as well as unique mouse models that have been generated by the INIAstress Consortium, including BXD Rl strains and conditional (inducible) knockout mice with targeted gene deletions. This will provide critical information for guiding more in-depth analyses (endocrine, neurochemical, electrophysiological, genetic/genomic) in other research components of the INIAstress Consortium. In this way, the Core serves a centralized function in not only informing other projects about optimal experimental parameters regarding CIE/stress interactions in various mouse genotypes, but it also creates a framework that will facilitate integration of diverse research findings from various INIAstress projects relevant to the overall research theme and goals of the Consortium.

描述（由申请人提供）：虽然应激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，但这些研究得出了模棱两可的结果，其结果取决于无数因素，包括使用的应激源类型、应激呈现时间、初始乙醇偏好等。INIAstress Consortium对这一文献做出了贡献，主要证明了各种应激源的急性/亚慢性管理导致各种小鼠模型中乙醇摄入的抑制。相反，我们实验室的结果表明，慢性间歇乙醇（CIE）暴露的反复循环确实会导致C57BL/6J小鼠自愿饮酒的增加。此外，很明显，CIE暴露的重复周期本身构成了一个强大的应激源，在神经和生理系统中产生深刻的干扰。这导致了一个总体概念，即慢性乙醇暴露和戒断经验会在应激和奖励回路内的神经生理系统中产生持续的扰动，从而使生物体不堪重负，超出正常的内稳态限制（即，一种非稳态状态）。这些神经适应被认为不仅影响应激反应，而且在驱动/促进与依赖相关的过量饮酒方面发挥作用。该小鼠CIE核心的一个主要目标是为各种遗传小鼠模型中乙醇依赖（CIE暴露）和应激对自愿乙醇摄入的影响提供全面的行为表型评估，并提供器官组织样本（例如脑，血浆，肾上腺）用于其他INIAstress项目。具体来说，本核心的研究将侧重于描述CIE暴露单独以及与各种应激程序相结合对依赖和非依赖动物自愿饮酒的影响。这些研究将在C57BL/6小鼠以及INIAstress Consortium生成的独特小鼠模型中进行，包括BXD Rl菌株和靶向基因缺失的条件（诱导）敲除小鼠。这将为指导INIAstress联盟其他研究组成部分的更深入的分析（内分泌、神经化学、电生理、遗传/基因组）提供关键信息。通过这种方式，核心不仅可以为其他项目提供关于各种小鼠基因型中CIE/应激相互作用的最佳实验参数的信息，而且还可以创建一个框架，促进与联盟整体研究主题和目标相关的各种INIAstress项目的各种研究成果的整合。