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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，压力是精神疾病病因或恶化的一个因素，并在其中起着重要作用