The Amygdala and Amphetamine Self-Administration

描述（由申请人提供）： 啮齿类动物自我给药是研究兴奋剂滥用机制和潜在治疗的一种有用技术。先前的研究表明，与相对不活跃的大鼠（低反应者）相比，在新环境中高度活跃的大鼠（高反应者）的兴奋剂自我给药更大。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刺激性自我给药更大。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。所提出的一组实验的整体机制框架是基于杏仁核（ACe）在调节唤醒由于其广泛的皮质和皮质下的预测的作用。我们假设，ACe是更活跃的高反应大鼠相比，低反应大鼠和大鼠饲养在一个孤立的条件相比，丰富的条件。将测量ACe的鹅膏蕈氨酸损伤对随后的安非他明自我给药的影响。此外，还将测量ACe中c-Fos标记的量，以确定ACe在易于自我给药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.