The Amygdala, Individual Differences, and Conditioned Hyperactivity

描述（由申请人提供）：大量研究表明，喜欢新奇或刺激的人（如高感觉寻求者）比低感觉寻求者更频繁地使用药物。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。本研究的长期目标是通过动物模型确定偏好新奇刺激和刺激性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）相比，在新环境中高度活跃的大鼠（高反应者）对安非他明诱导的运动活动更敏感，并且自我施用更多的安非他明。先前的研究表明，杏仁核中央核（ACe）的失活仅在高反应大鼠中减少安非他明的自我给药。这组实验的整体机制框架是基于ACe在调节觉醒中的作用，这是由于其广泛的皮层和皮层下投射。假设是高反应大鼠的ACe比低反应大鼠更活跃。将测量ACe失活对随后安非他明诱导的运动活动的影响，以确定ACe是否有助于提高高反应大鼠对安非他明诱导的运动活动的敏感性。此外，在与安非他明相关的环境中，条件活动的数量将被测量，以确定ACe是否有助于条件活动，以及高反应大鼠和低反应大鼠在条件活动上是否存在差异。此外，将测量ACe中c-fos的表达量，以确定高反应大鼠的ACe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。

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.