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: 6509120
• 负责人: Glenn R Valdez
• 金额: $ 2.52万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6509120
• 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.

拟议的研究的目的是研究慢性ETOH治疗对CRF系统的影响，以及该系统参与ETOH戒断综合征和ETOH奖励。 CRF调节HPA轴的激素，有助于保存体内平衡。 通过ETOH自我给药来破坏其正常分泌，可能会对生物的生存产生严重的后果。 在特定目标1下提出的实验将通过探索HPA轴的CRF调节基础的特定神经底物来提高对偏腔丘脑CRF系统功能的神经生物学变化和HPA轴的理解。 ETOH戒断综合征的主要特征是戒断产生的类似抗焦虑样反应。 在特定目标2下提出的实验将检查通过CRF系统的拮抗作用对EtOH撤回的单个和重复发作的焦虑样反应的衰减。 此外，依赖性似乎是维持寻求酒精行为的重要因素。 由于发现焦虑对酒精中毒中饮酒的复发产生了重大影响，因此在特定目标3下概述的实验将进一步研究CRF在介导依赖之后ETOH的奖励特性中的作用。