CHRONIC STRESS AND SYMPATHETIC RESPONSES

慢性压力和交感神经反应

基本信息

批准号：
3377800
负责人：
RICHARD C MCCARTY
金额：
$ 10.78万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-09-01 至 1988-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3377800
关键词：
adrenal medulla blood chemistry cardiovascular function catecholamines dosage epinephrine immobilization of body part insulin neural information processing neurotransmitter metabolism nicotine norepinephrine psychological adaptation psychological stressor stress sympathetic nervous system

项目摘要

In this proposal, I have outlined a program of research which focuses on homeostatic regulation of the sympathetic nervous system of laboratory rats during chronic exposure to stressful stimulation. The stress concept was first introduced by Hans Selye nearly 50 years ago. In spite of extensive research on the stress responses of animals and humans over the years, there remains a glaring absence of a soundly developed and widely accepted theoretical framework for this field of research. In this proposal, several experiments are described which will clarify the underlying adaptive responses of the sympathetic nervous system to acute versus chronic exposure to stressful stimulation. In the first experiment, adult male laboratory rats will be stressed 30 minutes per day for 0, 1, 7, 14, or 28 consecutive days in one of the following conditions: immobilization (IM), exposure to intermittent, inescapable footshock (FS), or immersion in 18 degrees C water (CI). To control for the element of predictability, another group of rats will be exposed randomly to 1 of the 3 stressors for 7, 14, or 28 consecutive days. Plasma levels of norepinephrine and epinephrine will be measured in blood samples taken before, during, and after stressful stimulation as an index of sympathetic-adrenal medullary activity. In addition, the effects of these stress regimens on catecholamine biosynthetic enzyme activities and catecholamine content of several sympathetically innervated tissues will be quantified. In a second series of "Cross-over" experiments, rats will be stressed chronically in one condition and then acutely in another (i.e. chronic IM-acute FS; chronic FS-acute CI; chronic CI-acute IM) to examine the sympathetic responsiveness of a chronically stressed animal to a novel stressor. The results of this research will provide an extensive empirical base for refining and extending the conceptualization of stress. In addition, it will serve as a foundation for directing the research efforts of my laboratory toward the study of central neuronal adaptations to stressful stimulation in laboratory animals. These findings will be of direct relevance to several stress-related disorders in humans, including peptic ulcer disease, hypertension, depression and coronary artery disease.

在这个提案中，我概述了一个研究计划，重点是实验大鼠交感神经系统的稳态调节长期暴露于压力刺激期间。应力的概念是近 50 年前由 Hans Selye 首次提出。尽管广泛多年来对动物和人类应激反应的研究，仍然明显缺乏健全发展和广泛接受的该研究领域的理论框架。在这个提案中，描述了几个实验，这将澄清潜在的问题交感神经系统对急性和急性应激反应的适应性反应长期暴露于压力刺激。在第一个实验中，成人雄性实验鼠每天承受压力 30 分钟，持续 0、1、7、14、或连续 28 天处于以下情况之一：不活动 (IM)、暴露于间歇性、不可避免的足部震动 (FS) 或浸入水中 18 摄氏度水 (CI)。为了控制可预测性因素，另一组老鼠将随机暴露于 3 种压力源中的一种连续 7、14 或 28 天。血浆去甲肾上腺素水平和将在之前、期间和期间采集的血液样本中测量肾上腺素应激刺激后作为交感肾上腺髓质指标活动。此外，这些应激疗法对儿茶酚胺生物合成酶活性及儿茶酚胺含量一些交感神经支配的组织将被量化。一秒钟在一系列“交叉”实验中，老鼠将长期处于压力之下一种病症，然后另一种病症急性发作（即慢性 IM-急性 FS；慢性 FS-急性 CI；慢性 CI-急性 IM）检查交感神经长期承受压力的动物对新压力源的反应。这这项研究的结果将为以下方面提供广泛的实证基础：完善和扩展压力的概念。此外，它将作为指导我的研究工作的基础实验室致力于研究中枢神经元对压力的适应对实验动物的刺激。这些发现将直接与人类多种压力相关疾病的相关性，包括消化道疾病溃疡病、高血压、抑郁症和冠状动脉疾病。