CHRONIC STRESS AND SYMPATHETIC RESPONSES

在这个建议中，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 在长期暴露于压力刺激下。 压力的概念是 由汉斯·塞利在50年前首次提出。 尽管广泛 多年来对动物和人类压力反应的研究， 仍然明显缺乏一个健全的发展和广泛接受的 这一研究领域的理论框架。 在这一提议中， 描述了几个实验，这些实验将阐明基本的 交感神经系统对急性和慢性炎症的适应性反应 长期暴露于压力刺激。 在第一个实验中，成年人 雄性实验室大鼠每天应激30分钟，持续0，1，7，14， 或在以下条件之一下连续28天： (IM)，暴露于间歇性，不可避免的脚震（FS），或浸泡在 18摄氏度的水（CI）。 为了控制可预测性， 将另一组大鼠随机暴露于3种应激源之一， 7、14或28天。 血浆去甲肾上腺素水平和 肾上腺素将在术前、术中和术后采集的血样中进行测量。 应激刺激后作为交感神经-肾上腺髓质 活动 此外，这些应激方案对 儿茶酚胺生物合成酶活性和儿茶酚胺含量 将量化几个交感神经支配的组织。 在第二 一系列的“交叉”实验，大鼠将长期应激， 一种情况，然后在另一种情况下急性（即慢性IM-急性FS; 慢性FS-急性CI;慢性CI-急性IM）检查交感神经系统 慢性应激动物对新应激源的反应性。 的 这项研究的结果将提供广泛的经验基础， 提炼和扩展压力的概念。 此外还 将作为指导我的研究工作的基础， 实验室对中枢神经元适应压力的研究 在实验室动物的刺激。 这些发现将直接 与人类的几种应激相关疾病相关，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.