CORTICOTROPIN RELEASING FACTOR, STRESS AND ADDICTION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。压力被认为是与可卡因成瘾相关的适应不良行为的主要因素。在人类和动物模型中，压力已被证明会导致吸毒增加和戒毒后复吸。戒断会导致焦虑样行为以及其他与压力反应相关的措施增加。促肾上腺皮质激素释放因子（corticotropinreleasing factor，CRF）是内分泌、自主神经和行为对应激刺激的主要协调者，与可卡因戒断相关的焦虑有直接关系。杏仁中央核（CeA）和终纹床核（BNST）是CRF的主要下丘脑外来源，并且已被证明在与可卡因成瘾和应激诱导的复发相关的行为中起关键作用。本提案的目标是从CeA和BNST中描绘CRF对可卡因诱导的脑效应和行为的特定作用。药理学方法加上腺相关病毒载体介导的RNA干扰，以敲低表达的CRF与焦点和时间分辨率将允许调查可卡因奖励和复发相关的问题。这个建议的目的是了解CRF介导的神经机制的具体方面与可卡因成瘾和应激诱导的可卡因寻求复发相关的适应不良行为。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Stress is thought to be a major factor underlying maladaptive behaviors associated with cocaine addiction. In both humans and animal models, stress has been shown to cause both increased use and relapse after detoxification. Cocaine withdrawal causes increased anxiety-like behavior as well as other measures associated with stress responses. Corticotropin releasing factor (CRF) is a major coordinator of endocrine, autonomic and behavioral output to stressful stimuli and CRF has been directly implicated in anxiety associated withdrawal from cocaine. The central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) are major extrahypothalamic sources of CRF and both have been shown to play critical roles in behaviors associated with cocaine addiction and stress-induced relapse. The goals of this proposal are to delineate the specific role of CRF from the CeA and BNST on cocaine-induced effects in brain and on behavior. A pharmacological approach coupled with adeno-associated viral vector-mediated RNA interference to knockdown expression of CRF with focal and temporal resolution will allow an investigation of questions related to cocaine reward and relapse. The aims of this proposal are to understand specific aspects of CRF-mediated neural mechanisms underlying maladaptive behaviors associated with cocaine addiction and stress-induced relapse to cocaine seeking.