The Amygdala and Amphetamine Self-Administration

描述(由申请人提供)： 啮齿类动物的药物自我给药是研究兴奋剂滥用的机制和可能的治疗方法的有用技术。先前的研究表明，在新环境中高度活跃的大鼠(高反应者)比相对不活跃的大鼠(低反应者)的刺激性自我管理更强。此外，与在丰富环境中长大的大鼠相比，在隔离环境中长大的大鼠的刺激性自我管理更强。本申请中提出的实验将确定由于遗传或环境因素而倾向于自我给药苯丙胺的大鼠是否具有过度活跃唤醒系统的共同神经特征。拟议的一系列实验的整体机制框架是基于杏仁中央核(ACEs)的广泛皮质和皮质下投射在调节觉醒中的作用。我们假设，与低反应者相比，高反应者大鼠的ACE活性更高，与丰富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。将测量鹅膏油酸损伤ACE对随后苯丙胺自我给药的影响。此外，将在ACEs中测量c-Fos标记量，以确定ACEs在那些倾向于自我给药苯丙胺的大鼠中是否具有更大的活性。这些实验的发现旨在促进对兴奋剂滥用脆弱性的理解，并可能导致更好的预防和治疗干预措施。

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.