Stress-induced alterations in amygdala-LC interactions

压力引起的杏仁核-LC 相互作用的改变

• 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
• 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

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.

已知压力是对精神疾病的病因或加剧的因素，并且发挥了 在恢复吸毒行为中的重要作用。该建议将主要使用电生理学 - 麻醉大鼠中的Al记录，以检查急性和慢性应激对调节的影响 杏仁核综合体的基因座（LC）。去甲肾上腺素和皮质激素释放激素 已被确定为应激响应的核心因素。特别是去甲肾上腺素能神经元 已知LC在压力反应的中央介导中具有重要作用。这些神经元是 受许多传入影响驱动。一组似乎在 与精神疾病有关的压力和对药物滥用的复发是涉及的预测 杏仁核。我们建议检查LC神经元活性的杏仁核调节，以及该系统如何 通过急性和慢性应激修饰。我们的中心假设是慢性应激会引起敏感性 LC神经元反应性通过其对杏仁核途径的影响。这将按照四个特定 目的：1）检查连接基底外侧杏仁核复合物的投影系统的生理 使用LC，2）检查该系统对急性应激源（脚震）的响应，以及这些系统如何 慢性冷暴露后，反应得到改变，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反应性的改变是否 在慢性应激之后，可以通过选择性中断这些杏仁核侵蚀来改变。我们将使用 主要是体内单个单元和细胞内记录方法，以检查系统级相互作用， 用体外记录用于测量LC神经元活动的持续变化并解决 出现的特定途径相关问题。我们将独立验证 通过测量声音惊吓来慢性冷暴露，这种反应对操纵的敏感 中央杏仁核和前脑NE系统。我们希望对杏仁核有更好的理解 - COERULEAR系统将导致对压力诱导的这些途径中的病理生理学的见解， ）艺术，调解精神病和药物滥用疾病的某些行为症状。