CHRONIC STRESS AND SYMPATHETIC RESPONSES

在这份提案中，我概述了一项研究计划，重点是 实验大鼠交感神经系统的动态平衡调节 在长期暴露于应激刺激的过程中。压力的概念是 汉斯·塞尔耶在近50年前首次提出了这一概念。尽管有广泛的 多年来对动物和人类应激反应的研究， 仍然明显缺乏一个完善的、被广泛接受的 这一领域研究的理论框架。在这份提案中， 描述了几个实验，这些实验将澄清潜在的 交感神经系统对急性VS的适应性反应 长期暴露在有压力的刺激下。在第一个实验中，成年的 雄性实验大鼠每天应激30分钟，持续0，1，7，14， 或者有下列情形之一的连续28天： (IM)、间歇性暴露、不可避免的足底电击(FS)或沉浸在 18摄氏度水(CI)。为了控制可预测性元素， 另一组大鼠将随机暴露于三种应激源中的一种 连续7天、14天或28天。血浆去甲肾上腺素和 肾上腺素将在采血前、采血期间和采血中进行测量。 应激刺激后作为交感-肾上腺髓质的指标 活动。此外，这些压力养生法对 大豆儿茶酚胺生物合成酶活性及儿茶酚胺含量 将对几个交感神经支配的组织进行量化。一秒钟内 系列“交叉”实验，大鼠将被慢性应激 一种情况，然后在另一种情况下(即慢性IM-急性FS； 慢性FS-急性脑梗塞；慢性脑梗塞-急性IM)检查交感神经 长期应激动物对新应激源的反应。这个 本研究的结果将为以下工作提供广泛的经验基础 提炼和延伸压力的概念。此外，它还 将作为指导我的研究工作的基础 中枢神经元对应激适应研究的实验室 对实验动物的刺激。这些发现将是直接的 与人类几种应激相关疾病的相关性，包括消化性疾病 溃疡病、高血压、抑郁症和冠状动脉疾病。

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.