CORTICOTROPIN RELEASING FACTOR IN THE CENTRAL NUCLEUS OF THE AMYGDALA IN STRESS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。应激诱发的精神病态是影响社会的主要问题。从创伤后应激障碍(PTSD)、抑郁和睡眠失调到上瘾后的失误和复发，所有这些疾病都有压力作为病因。这些由压力引起的疾病背后的机制还知之甚少。促肾上腺皮质激素释放因子(CRF)是大脑中的一个分子，被认为是生物体-S-适应性应激反应的主要协调者-包括内分泌、自主神经和行为反应。CRF介导的应激反应涉及许多脑区。杏仁中央核(CEA)是下丘脑外CRF的主要来源，参与调节对恐惧和焦虑的行为、情绪和生理反应。本项目的目的是阐明CEA中促肾上腺皮质激素释放因子(CRF)在中枢应激反应中的具体作用。学生将参与具体的实验，在这些实验中，我们将：1.确定CEA的CRF是否参与调节压力诱导的和类似焦虑的行为。RNA干扰(RNAi)将被用来局部沉默成年大鼠双侧CEA中CRF的表达。然后，这些大鼠将接受一系列行为模式的测试，以测量运动和类似焦虑的行为。这些测试包括开场测试、高架加迷宫、明暗盒子和声学惊吓。2.确定使用RNAi下调CEA中CRF的表达是否会降低应激反应中神经内分泌和自主神经激活的指标。心率和血压将使用无线电遥测进行监测。还将测量循环中皮质酮和促肾上腺皮质激素(ACTH)的水平。

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-induced psychopathologies are major problems affecting society. Disorders ranging from post-traumatic stress disorder (PTSD), depression and sleep dysregulation to lapse and relapse in addiction all have stress as an etiological factor. The mechanisms underlying these stress-induced disorders are poorly understood. Corticotropin releasing factor (CRF) is a molecule in brain that has been implicated as a primary coordinator of an organism?s adaptive stress responses - including endocrine, autonomic and behavioral responses. Numerous brain regions have been implicated in CRF mediated stress responses. The central nucleus of the amygdala (CeA) is a major extrahypothalamic source of CRF and is known to mediate behavioral, emotional and physiological responses to fear and anxiety. The goals of this project are to elucidate the specific role of corticotropin releasing factor (CRF) from the CeA in central responses to stress. Students will be involved in specific experiments in which we will: 1. Determine if CRF from the CeA is involved in mediating stress-induced and anxiety-like behaviors. RNA interference (RNAi) will be used to locally silence CRF expression bilaterally in the CeA of adult rats. The rats will then be put through a battery of behavioral paradigms to measure motor and anxiety-like behaviors. These tests include the open field test, elevated plus maze, light-dark box, and acoustic startle. 2. Determine if knocking down CRF expression from the CeA using RNAi decreases measures of neuroendocrine and autonomic activation in response to stress. Heart rate and blood pressure will be monitored employing radiotelemetry. Circulating levels of corticosterone and adrenocorticotropic hormone (ACTH) will also be measured