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.

已知压力是精神障碍的病因学或恶化的因素，并且在精神障碍的发病中起作用。 在恢复吸毒行为方面发挥重要作用。该提案将主要使用电生理学- 在麻醉大鼠中的al记录，以检查急性和慢性应激对 杏仁核复合体对蓝斑的影响。去甲肾上腺素和促肾上腺皮质激素释放激素 被认为是应对压力的核心因素。尤其是去甲肾上腺素能神经元 已知LC在应激反应的中枢介导中具有重要作用。这些神经元 由一系列的传入影响所驱动。有一组传入神经似乎在 与精神障碍和药物滥用复发有关的压力是涉及 杏仁核我们建议检查杏仁调节LC神经元的活动，以及这个系统是如何 受到急性和慢性压力的影响。我们的核心假设是慢性压力会导致 LC神经元反应性的影响。这将在沿着四个具体的 目的：1）研究杏仁核基底外侧复合体投射系统的生理学特征 2）检查该系统对急性应激源（足电击）的反应，以及这些应激源是如何产生的。 在慢性冷暴露后改变反应，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 通过选择性地中断这些杏仁核传出神经，可以改变慢性应激后的神经元的活动。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水平的相互作用， 体外记录用于测量LC神经元活动的持续变化， 具体的路径相关的问题，因为他们出现。我们将独立验证 慢性冷暴露通过测量声惊吓，一种反应，是敏感的操纵的 中央杏仁核和前脑NE系统。我们希望更好地了解杏仁核- 蓝斑系统将导致深入了解如何在这些途径的压力诱导的病理生理学， ART介导精神疾病和药物滥用障碍的一些行为症状。