The Amygdala and Amphetamine Self-Administration

杏仁核和安非他明自我管理

• 批准号: 6668460
• 负责人: Mary Eileen Cain
• 金额: $ 4.48万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-10-01 至 2004-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668460
• 关键词: amphetamines; amygdala; arousal; behavioral /social science research tag; gene expression; ibotenate; immunocytochemistry; laboratory rat; neuropharmacology; neurophysiology; neurotoxicology; postdoctoral investigator; protooncogene; psychopharmacology; self medication

DESCRIPTION (provided by applicant): Drug self-administration in rodents is a useful technique to examine the mechanisms and potential treatment of stimulant abuse. Previous research has shown that stimulant self-administration is greater in rats that are highly active in a novel environment (high responders) compared to rats that are relatively inactive (low responders). In addition, stimulant self-administration is greater in rats raised in an isolated environment compared to rats raised in an enriched environment. The experiments proposed in the present application will determine if rats that are prone to self-administer amphetamine, due to genetic or environmental factors, share a common neural profile of an overactive arousal system. The overall mechanistic framework for the proposed set of experiments is based on the role of the central nucleus of the amygdala (ACe) in regulating arousal due to its extensive cortical and subcortical projections. We hypothesize that the ACe is more active in high responder rats compared to low responder rats and in rats reared in an isolated condition compared to an enriched condition. The effects of ibotenic acid lesions of the ACe on subsequent amphetamine self-administration will be measured. In addition, the amount of c-Fos labeling will be measured in the ACe to determine if the ACe has greater activity in those rats prone to self-administer amphetamine. The findings from these experiments are intended to advance the understanding of vulnerability for stimulant abuse, and will potentially lead to better prevention and treatment interventions.

描述（由申请人提供）： 啮齿动物的自我给药是检查兴奋剂滥用的机制和潜在治疗方法的有用技术。先前的研究表明，与相对不活跃的老鼠（低反应者）相比，在新环境中高度活跃的老鼠（高反应者）自我给予兴奋剂的程度更高。此外，与在丰富环境中饲养的大鼠相比，在隔离环境中饲养的大鼠的自我兴奋剂施用量更大。本申请中提出的实验将确定由于遗传或环境因素而易于自我施用安非他明的大鼠是否具有过度活跃的唤醒系统的共同神经特征。所提议的一组实验的总体机制框架基于杏仁核中央核（ACe）由于其广泛的皮质和皮质下投射而在调节唤醒中的作用。我们假设，与低反应大鼠相比，高反应大鼠中的 ACe 更活跃；与在富集条件下饲养的大鼠相比，在隔离条件下饲养的大鼠中 ACe 更活跃。将测量 ACe 的鹅膏蕈酸损伤对随后的安非他明自我给药的影响。此外，将测量 ACe 中 c-Fos 标记的量，以确定 ACe 在那些倾向于自我施用安非他明的大鼠中是否具有更大的活性。这些实验的结果旨在增进对兴奋剂滥用脆弱性的了解，并有可能带来更好的预防和治疗干预措施。