CHRONIC STRESS AND SYMPATHETIC RESPONSES

慢性压力和交感神经反应

• 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
• 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

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.

在此提案中，我概述了一项研究计划，该计划的重点是 实验室大鼠交感神经系统的稳态调节 在长期暴露于压力刺激期间。 压力概念是 大约50年前，汉斯·塞利（Hans Selye）首次提出。 尽管有广泛的 多年来对动物和人类的压力反应的研究， 仍然没有一个明显的发达和广泛接受的 该研究领域的理论框架。 在此提案中， 描述了几个实验，这些实验将阐明基础 交感神经系统对急性与急性的自适应反应 长期暴露于压力刺激。 在第一个实验中，成人 男性实验室大鼠每天将压力为0、1、7、14， 在以下条件之一中连续28天：固定 （IM），接触间歇性，不可避免的脚印（FS）或沉浸在 18度C水（CI）。 为了控制可预测性元素， 另一组大鼠将被随机暴露于3个应激源中的1个 连续7、14或28天。 去甲肾上腺素的血浆水平和 肾上腺素将在之前，期间，期间和 在压力刺激后，作为交感神经 - 肾上腺髓质的指数 活动。 另外，这些应力方案对 儿茶酚胺生物合成酶活性和儿茶酚胺含量 将量化几种交感神经化的组织。 一秒钟 一系列“交叉”实验，大鼠将长期压力 一种条件，然后在另一个条件中敏锐（即慢性肌fs； 慢性FS急性CI；慢性ci急性IM）检查同情 长期压力动物对新型压力源的反应。 这 这项研究的结果将为广泛的经验基础提供 完善和扩展压力的概念化。 另外，它 将作为指导我的研究工作的基础 实验室研究中央神经元适应压力 实验动物刺激。 这些发现将是直接的 与人类中的几种与压力有关的疾病的相关性，包括消毒 溃疡病，高血压，抑郁和冠状动脉疾病。