The Amygdala, Individual Differences, and Conditioned Hyperactivity

描述(由申请人提供)：大量研究表明，喜欢新奇刺激或唤起刺激的人(例如，高感觉寻求者)比低感觉寻求者更频繁地使用毒品。因此，高感觉寻求者可能在生物学上倾向于发现新的刺激和药物比低感觉寻求者更有回报。这项研究的长期目标是通过动物模型确定喜欢新奇刺激和唤醒刺激的个体是否具有共同的神经解剖学机制。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)对苯丙胺诱导的运动活动更敏感，自我管理的苯丙胺更多。先前的研究表明，杏仁中央核(ACEs)的失活只会减少高反应性大鼠的苯丙胺自我给药。拟议的一系列实验的整体机制框架是基于ACE在调节唤醒方面的作用，因为它具有广泛的皮质和皮质下投射。假说是，与低反应大鼠相比，高反应大鼠的ACE更活跃。将测量ACE失活对随后苯丙胺诱导的运动活动的影响，以确定ACE是否有助于提高高反应性大鼠对苯丙胺诱导的运动活动的敏感性。此外，将测量苯丙胺相关环境中的条件性活动量，以确定ACE是否有助于条件性活动，以及高反应者和低反应者大鼠的条件性活动是否不同。此外，还将测量ACE中c-fos的表达量，以确定ACE在高反应性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): Numerous studies suggest that people who prefer novel or arousing stimulation (e.g. high sensation- seekers) use drugs more frequently than low sensation seekers. Thus, high sensation-seekers may be predisposed biologically to find both novel stimuli and drugs to be more rewarding than low sensation- seekers. The long-term goal of this research is to determine if individuals who prefer novel and arousing stimuli share a common neuroanatomical mechanism using an animal model. Rats that are highly active in a novel environment (high responders) are more sensitive to amphetamine-induced locomotor activity and self-administer more amphetamine compared to rats that are relatively inactive (low responders). Previous research has demonstrated that inactivation of the central nucleus of the amygdala (ACe) reduces amphetamine self-administration only in high responder rats. The overall mechanistic framework for the proposed set of experiments is based on the role of the ACe in regulating arousal due to its extensive cortical and subcortical projections. The hypothesis is that the ACe is more active in high responder rats compared to low responder rats. The effects of inactivation of the ACe on subsequent amphetamine- induced locomotor activity will be measured to determine if the ACe contributes to the increased sensitivity of high responder rats to amphetamine-induced locomotor activity. Further, the amount of conditioned activity in an amphetamine-associated environment will be measured to determine if the ACe contributes to conditioned activity and if high responder and low responder rats differ in conditioned activity. In addition, the amount of c-fos expression will be measured in the ACe to determine if the ACe has greater activity in high responder rats. The findings of these experiments are intended to advance the understanding of vulnerability for stimulant abuse, and will potentially lead to better prevention and treatment interventions.