Role of Amygdala in Ethanol Reinforcement and Anxiety

杏仁核在乙醇强化和焦虑中的作用

• 批准号: 6795320
• 负责人: AMANDA J ROBERTS
• 金额: $ 17.44万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6795320
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; amygdala; anxiety; behavioral /social science research tag; cooperative study; corticotropin releasing factor; disease /disorder model; drug withdrawal; ethanol; genetically modified animals; laboratory mouse; neuropsychology; opioid receptor; reinforcer; relapse /recurrence; self medication; substance abuse related behavior

One of the primary goals of this 1NIA is to identify behavioral neuroadaptations that occur in the brain reward circuits associated with the extended amygdala and its connections that result in excessive ethanol consumption. In these proposed experiments, a model of excessive ethanol self-administration will be applied to several mouse lines/strains that have unique genotypes hypothesized to be related to the link between ethanol self-administration and extended amygdala function (anxiety-like behaviors and reward function following dependence). Mice will be trained to self-administer ethanol in an operant paradigm, made dependent using an ethanol-containing liquid diet and then exposed to operant ethanol self-administration during repeated bouts of withdrawal. It is predicted that the development of an association between ethanol self-administration and the attenuation of affective withdrawal symptoms will result in excessive ethanol consumption. It is hypothesized that withdrawal is associated with increased I anxiety-like behavior and increased responsiveness to stressor exposure and that both contribute to increasing ethanol consumption in dependent animals. In addition, neurochemistry within the extended amygdala (central and medial nuclei of the amygdala and the BNST) will be manipulated in order to more directly characterize the role of this circuitry in excessive ethanol consumption. It is hypothesized that the corticotropin releasing factor (CRF) and opioid systems in the amygdala are involved in excessive ethanol self-administration and anxiety-like behavior in dependent mice. The implication from these findings is that the control of anxiety in alcoholics is extremely important in reducing relapse. The investigation of neuronal systems that mediate anxiety with regard to their contribution to alcohol self- administration may ultimately lead to more effective treatment approaches to the chronically relapsing disease of alcoholism. This INIA makes use of several Genetic Animal Models Core Components, relates well to other INIA UOls, and also will provide input to the Gene Expression, Imaging and the Bioinformatics Cores.

该1NIA的主要目标之一是识别大脑中发生的行为神经照射，这些行为神经适应与扩展的杏仁核相关的电路及其连接，从而导致过量的乙醇消耗。在这些提出的实验中，过度乙醇自我给药的模型将应用于几种具有独特基因型的小鼠线/菌株，该基因型与乙醇自我给药和扩展的杏仁核功能（焦虑般的行为和类似奖励功能）相关的唯一基因型以下依赖）。小鼠将接受训练以在操作范式中自助乙醇的培训，使用含有乙醇的液体饮食依赖，然后在反复退出时暴露于操作的乙醇自我管理。据预测，乙醇自我给药与情感戒断症状的衰减之间的关联将导致过度消耗乙醇。假设戒断与I焦虑样行为增加和对压力源暴露的反应性增加有关，并且两者都有助于增加依赖动物的乙醇消耗。此外，将操纵扩展杏仁核内神经化学（杏仁核和BNST的中间核），以便更直接地表征该电路在过度乙醇消耗中的作用。假设杏仁核中的皮质激素释放因子（CRF）和阿片类药物系统参与了依赖小鼠的过度乙醇自我给药和焦虑样行为。这些发现的含义是，酗酒者对焦虑的控制对于减少复发极为重要。对介导其对酒精自我施用贡献的焦虑的神经元系统的研究最终可能会导致更有效的治疗方法，以使其长期复发的酒精中毒疾病。该INIA利用了几种遗传动物模型的核心成分，与其他Inia UOL息息相关，还将提供基因表达，成像和生物信息学核心的输入。