Role of CRF in ethanol negative reinforcement

CRF 在乙醇负强化中的作用

• 批准号: 6835509
• 负责人: CINDY K REITER
• 金额: $ 4.3万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-17 至 2008-01-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6835509
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; amygdala; behavior test; behavioral /social science research tag; compulsive behavior; corticotropin releasing factor; drug withdrawal; ethanol; hormone receptor; hormone regulation /control mechanism; laboratory rat; microdialysis; negative reinforcements; neurobiology; neurochemistry; neuropharmacology; postdoctoral investigator; protein quantitation /detection; receptor expression; relapse /recurrence; self medication

DESCRIPTION (provided by applicant): The neurobiological basis for the negative reinforcement important for the development of alcoholism and the vulnerability to relapse is believed to include counteradaptive neurochemical events within the brain emotional systems, such as the stress systems. Corticotropin releasing factor has been implicated in the motivational changes associated with ethanol withdrawal and the increased ethanol self-administration associated with withdrawal in the rat. CRF activity is recruited in alcohol dependent animals during withdrawal and protracted abstinence. Dependent animals also display enhanced stress-like responses and enhanced ethanol self-administration during acute withdrawal and protracted abstinence, effects reversed by CRF antagonists. The experiments in this proposal are designed to study the role of CRF1 and CRF2 receptors in specific brain regions in mediating the enhanced drinking associated with ethanol withdrawal. Further, the role of CRF2 receptors and CRF1 and CRF2 receptor expression in mediating the enhanced CRF release during ethanol withdrawal will be examined. The overall hypothesis is that increased CRF activity in the extended amygdala is responsible for the enhanced drinking associated with withdrawal.

描述（由申请人提供）：据信，对酒精中毒发展和复发的脆弱性重要的负强化的神经生物学基础被认为包括大脑情感系统（例如压力系统）内的反适应性神经化学事件。皮质激素释放因子与与乙醇的戒断相关的动机变化以及与大鼠戒断相关的乙醇自我给药的增加有关。 CRF活性在戒断和持久节制过程中募集在依赖酒精的动物中。依赖的动物还表现出增强的压力样反应，并在急性戒断和持久节制期间增强了乙醇自我给药，其效果与CRF拮抗剂相反。该提案中的实验旨在研究CRF1和CRF2受体在特定大脑区域中介导与乙醇戒断相关的增强饮酒方面的作用。此外，将研究CRF2受体，CRF1和CRF2受体表达在介导乙醇戒断过程中增强的CRF释放中的作用。总体假设是，扩展的杏仁核中CRF活性的增加负责与戒断相关的增强饮酒。