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.

众所周知，压力是精神疾病的病因或恶化的一个因素，并在 在恢复吸毒行为方面发挥重要作用。这项提议将主要使用电生理学- 急性应激和慢性应激对麻醉大鼠脑电活动调节的影响 杏仁复合体周围的蓝斑(LC)。去甲肾上腺素和促肾上腺皮质激素释放激素 已经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在应激反应的中枢调节中起着重要作用。这些神经元是 受一些传入影响的驱使。一组传入神经似乎在 压力与精神障碍和药物滥用复发有关，这些预测涉及 杏仁核。我们建议研究杏仁核对LC神经元活性的调节，以及这个系统是如何 受到急性和慢性压力的影响。我们的中心假设是慢性压力会引起敏感化 通过其对杏仁核通路的影响来研究LC神经元的反应性。这将沿着四个具体的步骤来完成 目的：1)检查连接杏仁基底外侧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(足底电击)的反应，以及这些反应如何 慢性冷暴露后的反应被修改，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 慢性应激可通过选择性阻断杏仁核的传出改变。我们将使用 主要是体内单一单位和细胞内记录方法，以检查系统级别的相互作用， 使用体外记录来测量LC神经元活动的持续变化并解决 出现特定的与路径相关的问题。我们将独立验证 通过测量声惊厥来测量慢性冷暴露，这是一种对操纵 中央杏仁核和前脑NE系统。我们希望对杏仁核有更好的了解- 蓝斑系统将引导人们深入了解应激诱导的这些通路中的病理生理学如何在 )ART，调解精神疾病和药物滥用障碍的一些行为症状。