CORTICOTROPIN RELEASING FACTOR, STRESS AND ADDICTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 压力被认为是导致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，压力都被证明会导致更多的使用和戒毒后的复发。戒掉可卡因会导致焦虑样行为增加，以及与压力反应相关的其他指标。促肾上腺皮质激素释放因子(CRF)是内分泌、自主神经和行为输出对应激刺激的主要协调者，CRF与焦虑相关的可卡因戒断直接相关。杏仁中央核(CEA)和终纹床核(BNST)是下丘脑外CRF的主要来源，两者都被证明在与可卡因成瘾和应激性复发相关的行为中发挥关键作用。这项提议的目的是从CEA和BNST中描绘CRF在可卡因诱导的大脑和行为中的具体作用。一种药理学方法与腺相关病毒载体介导的RNA干扰相结合，以局部和时间分辨率下调CRF的表达，将使研究与可卡因奖励和复发有关的问题成为可能。这项建议的目的是了解CRF介导的神经机制的特定方面，这些机制可能导致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.