Stress-induced alterations in amygdala-LC interactions

压力引起的杏仁核-LC 相互作用的改变

基本信息

批准号：
7618885
负责人：
ANTHONY A GRACE
金额：
$ 7.88万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7618885
关键词：
Acoustics Acute Address Affect Amygdaloid structure Animals Arts Behavior Behavioral Behavioral Symptoms Chronic Chronic stress Complex Corticotropin-Releasing Hormone Cyclic AMP Data Disease Drug abuse Electric Stimulation Etiology Exhibits Exposure to Fire - disasters Functional disorder Hippocampus (Brain)In Vitro Infusion procedures Interruption Investigation Lead Lesion Measures Mediating Mediation Mental disorders Methods N-Methylaspartate Nature Neurons Norepinephrine Numbers Pathway interactions Pharmaceutical Preparations Physiological Physiology Play Potassium Prosencephalon Rattus Regulation Relapse Role Second Messenger Systems Shock Stimulus Stress Structure of terminal stria nuclei of preoptic region System Tail Testing Time biological adaptation to stress day in vivo indexing insight locus ceruleus structure neurochemistry noradrenergic norepinephrine system novel prevent response sciatic nerve second messenger stressor

项目摘要

Stress is known to be a factor in the etiology or exacerbation of psychiatric disorders, and plays an important role in reinstatement of drug-taking behavior. This proposal will use primarily electrophysiologic- al recordings in anesthetized rats to examine the effects of acute and chronic stress on the regulation of the locus coeruleus (LC) by the amygdalar complex. Norepinephrine and corticotropin releasing hormone have been identified as central factors in the response to stress. In particular, the noradrenergic neurons of the LC are known to have a major role in central mediation of stress responses. These neurons are driven by a number of afferent influences. One set of afferents that appears to have a primary role in stress as it relates to psychiatric disorders and relapse to drug abuse are the projections that involve the amygdala. We propose to examine amygdalar regulation of LC neuron activity, and how this system is modified by acute and chronic stress. Our central hypothesis is that chronic stress causes a sensitization of LC neuron responsivity via its effects on amygdalofugal pathways. This will be done along four specific aims: 1) to examine the physiology of projection systems connecting the basolateral amygdala complex with the LC, 2) to examine the response of this system to acute stressors (footshock), and how these responses are modified following chronic cold exposure, 3) to evaluate the nature of the change in LC neuron responsivity following chronic stress, and 4) to determine whether the alteration in LC responsivity following chronic stress can be altered by selective interruption of these amygdalar efferents. We will use primarily in vivo single unit and intracellular recording methods to examine systems-level interactions, with in vitro recordings used to measure persistent changes in LC neuronal activity and to address specific pathway-related questions as they arise. We will independently verify the behavioral effects of chronic cold exposure by measuring acoustic startle, a response that is sensitive to manipulations of the central amygdala and forebrain NE systems. We hope that a better understanding of amygdalar- coerulear systems will lead to insights into how stress-induced pathophysiology in these pathways can, in )art, mediate some of the behavioral symptoms of psychiatric disease and drug-abuse disorders.

众所周知，压力是精神疾病的病因或恶化的一个因素，并且起着重要作用。在恢复吸毒行为方面发挥着重要作用。该提案将主要使用电生理学麻醉大鼠的所有记录，以检查急性和慢性应激对调节的影响蓝斑（LC）由杏仁核复合体控制。去甲肾上腺素和促肾上腺皮质激素释放激素已被确定为压力反应的核心因素。特别是去甲肾上腺素能神经元众所周知，LC 的功能在应激反应的中枢调节中发挥着重要作用。这些神经元是受多种传入影响的驱动。一组似乎在以下过程中起主要作用的传入神经：与精神疾病和药物滥用复发相关的压力是涉及以下因素的预测杏仁核。我们建议检查杏仁核对 LC 神经元活动的调节，以及该系统是如何运作的因急性和慢性压力而改变。我们的中心假设是慢性压力会导致过敏通过其对杏仁核通路的影响来影响 LC 神经元的反应性。这将通过四个具体步骤来完成目的：1）检查连接基底外侧杏仁核复合体的投射系统的生理学使用 LC，2) 检查该系统对急性应激源（足部休克）的反应，以及这些反应如何慢性寒冷暴露后反应会发生变化，3) 评估 LC 变化的性质慢性应激后的神经元反应性，以及 4) 确定 LC 反应性是否改变慢性压力后的情况可以通过选择性中断这些杏仁核传出神经来改变。我们将使用主要是体内单个单元和细胞内记录方法来检查系统级相互作用，体外记录用于测量 LC 神经元活动的持续变化并解决当出现具体的途径相关问题时。我们将独立验证以下行为的影响通过测量声学惊吓来长期暴露在寒冷中，这是一种对操纵的敏感反应中央杏仁核和前脑 NE 系统。我们希望更好地了解杏仁核核核系统将深入了解这些途径中应激诱导的病理生理学如何在）艺术，调解精神疾病和药物滥用障碍的一些行为症状。