Ethanol Dependence & Stress Effects on Ethanol Drinking

乙醇依赖

• 批准号: 7021416
• 负责人: HOWARD C. BECKER
• 金额: $ 24.68万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7021416
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; anxiety; behavior modification; behavioral /social science research tag; drug withdrawal; ethanol; genetic models; laboratory mouse; neuroendocrine system; psychological reinforcement; psychological stressor; self medication

DESCRIPTION (provided by applicant): A complex interplay among numerous biological and environmental factors govern both ethanol (EtOH) seeking and drinking behavior. Among these, genetics and stress certainly play prominent roles in shaping vulnerability and susceptibility for future problems with EtOH, as well as risk of developing alcoholism. While stress has been viewed as an important contributing factor to EtOH abuse and alcoholism, the interaction between stress and EtOH drinking behavior is not well understood. This is especially true when one considers the role/impact of stress on EtOH self-administration in the context of EtOH dependence. Chronic excessive consumption of EtOH can lead to the development of dependence, and repeated experience with associated withdrawal episodes may constitute a powerful motivational force that contributes to the perpetuation of EtOH use/abuse. Further, functional changes in brain/neuroendocrine stress and reward systems as a result of chronic EtOH exposure may render subjects not only more vulnerable to engage in excessive uncontrollable EtOH drinking, but also more susceptible to events (stress) that may trigger re-initiation of EtOH use after periods of abstinence (relapse). Unfortunately, little is known about the dynamics associated with the relationship between stress and EtOH consumption after dependence has been established. While a substantial emphasis of the existing NIAAA-supported "Stress, Anxiety and Alcohol Abuse" (WFUSM-INIA) Consortium is focused on elucidating the interaction of stress on EtOH consumption in various genetic mouse models, none of this work involves looking at the stress-EtOH relationship in dependent animals. The overall goal of this project is to utilize our established mouse model of EtOH dependence to investigate whether stress associated with repeated cycles of chronic EtOH exposure/withdrawal experience influences EtOH self-administration behavior, and whether such experience subsequently influences the ability of acute stress to modify EtOH seeking and drinking behavior. As such, this project not only fills a void in the literature related to EtOH dependence and stress, but importantly, it targets the major overarching theme of the WFUSM-INIA Consortium. Furthermore, the proposed work not only complements ongoing work in the Consortium, but it enhances the Consortium by expanding its focus to include the full spectrum of the addiction process, from use, to abuse, and to dependence. The overall goal of this proposal is to provide new information about the interaction between EtOH dependence, stress, and EtOH drinking behavior that is relevant to the WFUSM-IN1A Consortium, as well as the alcohol field in general.

描述（由申请人提供）：众多生物和环境因素之间复杂的相互作用控制着乙醇（EtOH）的寻求和饮用行为。其中，遗传和压力无疑在塑造未来乙醇问题的脆弱性和易感性以及酗酒的风险方面发挥着重要作用。 虽然压力被视为导致乙醇滥用和酗酒的重要因素，但压力与乙醇饮酒行为之间的相互作用尚不清楚。当人们考虑在乙醇依赖的情况下压力对乙醇自我给药的作用/影响时尤其如此。长期过量消耗乙醇会导致依赖性的发展，并且反复经历相关的戒断事件可能会构成强大的动力，导致乙醇使用/滥用的持续存在。此外，长期接触乙醇导致的大脑/神经内分泌压力和奖励系统的功能变化可能使受试者不仅更容易陷入过量、无法控制的乙醇饮酒，而且更容易受到可能触发重新开始的事件（压力）的影响。戒断一段时间后使用乙醇（复发）。不幸的是，人们对建立依赖性后压力与乙醇消耗之间关系的动态知之甚少。虽然现有 NIAAA 支持的“压力、焦虑和酒精滥用”(WFUSM-INIA) 联盟的重点是阐明压力对各种遗传小鼠模型中乙醇消耗的相互作用，但这些工作都没有涉及研究压力-EtOH 与依赖性动物的关系。该项目的总体目标是利用我们建立的乙醇依赖小鼠模型来研究与慢性乙醇暴露/戒断经历的重复循环相关的压力是否会影响乙醇的自我给药行为，以及这种经历是否会随后影响急性应激的能力。改变乙醇寻求和饮酒行为。因此，该项目不仅填补了与 EtOH 依赖和压力相关的文献空白，而且重要的是，它针对的是 WFUSM-INIA 联盟的主要总体主题。此外，拟议的工作不仅补充了联盟正在进行的工作，而且还通过将其重点扩大到包括成瘾过程的全部范围（从使用、滥用到依赖）来增强联盟。该提案的总体目标是提供有关 EtOH 依赖、压力和 EtOH 饮酒行为之间相互作用的新信息，这些信息与 WFUSM-IN1A 联盟以及整个酒精领域相关。