INTERACTIONS OF CRF AND NE IN NUCLEUS ACCUMBENS SHELL

描述(申请人摘要)：该系统的失调与抑郁症等精神疾病有关。CRF被认为是对应激的综合自主神经、神经内分泌和行为反应的中枢调节因子。CRF的行为效应通常类似于轻度应激或唤醒的情况；去甲肾上腺素(NE)被认为通过增强神经元感觉输入的突显来调节唤醒和警觉。因此，CRF和NE可以相互作用，调节生物体对其不断变化的环境条件所表现出的基本行为特征。伏隔核的壳亚区(AcbSh)含有密集的CRF和NE，被认为整合了皮质、边缘、自主和运动区处理的信息；因此，AcbSh非常适合调节有机体的基本行为特征，以响应其动态的外部环境。因此，AcbSh可能是CRF和NE系统在生物体基本行为调控中发挥作用并可能相互作用的重要部位。本提案旨在研究CRF和NE在AcbSh中的行为作用，以及该区域内这些系统之间可能相互作用的神经化学和解剖学基础。这项工作可能为描述有机体维持行为动态平衡的基本机制提供重要的第一步；对这些底物的理解最终可能有助于洞察一些在抑郁症和焦虑症等疾病中变得失控的过程，这些疾病的特征是对环境意外事件表现出不适当的行为反应。

DESCRIPTION (applicant's abstract): Dysregulation of the system has been associated with psychiatric disorders such as depression. CRF is thought to function as a central mediator of integrated autonomic, neuroendocrine, and behavioral responses to stress. The behavioral effects of CRF often resemble conditions of mild stress or arousal; norepinephrine (NE) has been proposed to regulate arousal and vigilance by enhancing the salience of sensory inputs to neurons. Thus, CRF and NE could interact to modulate the fundamental behavioral profile that an organism exhibits in response to its changing environmental conditions. The shell subregion of the nucleus accumbens (AcbSh) contains dense concentrations of CRF and NE, and is thought to integrate information processed in cortical, limbic, autonomic, and motor areas; AcbSh is thereby very well positioned to regulate the basic behavioral profile of an organism in response to its dynamic external milieu. AcbSh could thus be an important site in which CRF and NE systems act and possibly interact in the regulation of an organism's fundamental behavioral repertoire. The present proposal seeks to examine the behavioral roles of CRF and NE in the AcbSh, and the neurochemical and anatomical substrates of possible interactions between these systems within this region. This work may provide an important first step in characterizing the basic mechanisms through which an organism maintains behavioral homeostasis; understanding of these substrates might ultimately shed insight into some of the processes that become dysregulated in illnesses such as depression and anxiety disorders that are characterized by the expression of inappropriate behavioral responses to environmental contingencies.