Neural Mechanism by which Punishment Modulates Drug-Seeking

描述（由申请人提供）：成瘾行为的定义特征之一是它的持久性，尽管潜在的严重不良后果。为了进一步理解为什么成瘾者不能从消极结果中学习，我们建议探索一个新发现的大脑区域，即前内侧被盖核（RMTg）的作用，我们和其他人最近发现该区域编码消极奖励预测错误，并在各种厌恶行为中起关键作用

DESCRIPTION (provided by applicant): One of the defining features of addictive behavior is its persistence despite potentially severe adverse outcomes. To further understand why addicts fail to learn from negative outcomes, we propose to explore the role of a newly identified brain region, the rostromedial tegmental nucleus (RMTg), which we and others have recently shown to encode negative reward prediction errors, and to be critically involved in a variety of aversive behaviors. We hypothesize that impairment of this structure leads to an addiction phenotype in which animals persistently seek outcomes despite aversive outcomes. We propose two aims, the first of which is designed to better understand the basic mechanisms by which the RMTg contributes to learning about negative outcomes. Our second aim is more translational, exploring the role of the RMTg in cocaine-seeking under punishment, as well as its contribution to individual variation in propensity to develop addictive behaviors. PUBLIC HEALTH RELEVANCE: One hallmark of an addictive behavior is its persistence despite large negative outcomes, which can take a variety of forms, include physically aversive outcomes (withdrawal, toxicity) or social, cognitive, and financial losses. To better understand the pathology underlying these behaviors, we will explore the mechanisms underlying our recent findings that lesions of the rostromedial tegmental nucleus (RMTg) render animals strikingly deficient in learning from aversive outcomes. This will facilitate better treatments for behavioral disorders in which individuals seek drug rewards despite the large costs they incur.