ROLE OF CORTICOTROPIN RELEASING FACTOR IN ETHANOL WITHDR

促肾上腺皮质激素释放因子在乙醇戒断中的作用

• 批准号: 6371277
• 负责人: Glenn R Valdez
• 金额: $ 2.35万
• 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: 2001-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6371277
• 关键词: adrenocorticotropic hormone; alcoholism /alcohol abuse; amygdala; anxiety disorders; behavioral /social science research tag; corticosterone; corticotropin releasing factor; drug withdrawal; ethanol; hypothalamic pituitary adrenal axis; hypothalamus; laboratory rat; microdialysis; psychopharmacology; radioimmunoassay; reinforcer

The objective of the proposed studies is to investigate the influence of chronic EtOH treatment on the CRF system and the involvement of this system in the EtOH withdrawal syndrome and EtOH reward. CRF regulates hormones of the HPA axis, which aid in the preservation of homeostasis. Disruption of their normal secretion via EtOH self-administration could produce severe consequences for the organism's survival. Experiments proposed under Specific Aim 1 would advance the understanding of the neurobiological changes in the function of the extrahypothalamic CRF systems and the HPA axis resulting from chronic EtOH exposure by exploring the specific neural substrates underlying CRF regulation of the HPA axis. A major characteristic of the EtOH withdrawal syndrome is the anxiogenic-like response produced by withdrawal. Experiments proposed under Specific Aim 2 will examine the attenuation of the anxiogenic-like response to single and repeated episodes of EtOH withdrawal via antagonism of the CRF system. In addition, dependence appears to be an important factor in maintaining alcohol-seeking behavior. Since anxiety has been found to have a major influence on relapse of alcohol drinking in alcoholics, experiments outlined under Specific Aim 3 will further examine the role of CRF in mediating the rewarding properties of EtOH subsequent to dependence.

拟议研究的目的是调查慢性 EtOH 治疗对 CRF 系统的影响以及该系统在 EtOH 戒断综合征和 EtOH 奖励中的参与。 CRF 调节 HPA 轴的激素，有助于维持体内平衡。 通过乙醇自我给药破坏其正常分泌可能会对生物体的生存产生严重后果。 具体目标 1 下提出的实验将通过探索 CRF 调节 HPA 轴的特定神经底物，促进对慢性 EtOH 暴露引起的下丘脑外 CRF 系统和 HPA 轴功能的神经生物学变化的理解。 乙醇戒断综合征的一个主要特征是戒断产生的焦虑样反应。 具体目标 2 下提出的实验将通过对抗 CRF 系统来检查单次和重复 EtOH 戒断发作的焦虑样反应的减弱情况。 此外，依赖性似乎是维持饮酒行为的一个重要因素。 由于已发现焦虑对酗酒者的饮酒复发有重大影响，具体目标 3 中概述的实验将进一步研究 CRF 在调节 EtOH 依赖后的奖励特性中的作用。