RESPONSES TO CHRONIC STRESS IN MONKEYS

重要性慢性社会和心理应激源，普遍存在 在现代社会中，健康和福利是重要的决定因素。 这项研究调查了高度社会性的灵长类动物的后果 挑战修复的社会和环境扰动 动态平衡并导致长时间的 垂体-肾上腺调节。目标本研究计划是 旨在评估认知、免疫学和神经生物学 产生慢性抬高和慢性升高的压力源的后果 恒河猴脑下垂体-肾上腺活性降低。结果 慢性阻塞性肺疾病的免疫学和神经生物学研究 应激依赖于糖皮质激素的药理操作 级别。这项研究的假设是，它是由压力引起的 引起健康风险的糖皮质激素水平升高 在有压力的情况下，很少直接测试。我们的研究将 利用两种慢性压力模型，会产生截然不同的结果 各种形式的垂体-肾上腺功能失调。第一个慢性阻塞性肺疾病模型 压力，即重复的日常压力，已经被广泛用来理解 压力源的后果可能会随着时间的推移而积累。我们将每天使用 椅子束缚，一种身体和心理上的压力源 猴子的行为适应，但继续引发实质性的 垂体-肾上腺反应。试点数据表明，这种类型的 反复应激会导致基础皮质醇水平的慢性升高。 第二个压力源--社会不稳定--利用了广泛的 对猴子社会互动的认识和证据 这些猴子的社会环境的变化提供了 慢性压力的自然主义模型。与假设相反 关于身体压力的影响，社会不稳定 已被证明会导致基础皮质醇的长期减少。 两种慢性应激诱导模型的比较提供了一个 独一无二的机会来问慢性压力是否包含了 不同的症状，每一种都与自己的症状和风险相关。 未来的方向我们将开始详细的认知比较 性能(使用计算机辅助行为测试)和 慢性高血压病动物的免疫功能 糖皮质激素减少。计划还包括对海马区进行比较 慢性疲劳的动物的结构和功能 压力。关键词压力，皮质醇，垂体，肾上腺资金NIH 格兰特RR00169

Significance Chronic social and psychological stressors, prevalent in modern society, are important determinants of health and welfare. This research investigates in highly social primates, the consequences of social and environmental perturbations that challenge restoration of homeostasis and lead to lengthy periods of altered pituitary-adrenal regulation. Objectives This program of research is designed to evaluate the cognitive, immunological, and neurobiological consequences of stressors that produce chronic elevations and chronic reductions in pituitary-adrenal activity in rhesus monkeys. Results Much of the immunological and neurobiological research in chronic stress has relied on pharmacological manipulation of glucocorticoid levels. The assumption of this research, that it is stress-induced elevations in glucocorticoids that account for health risks associated with stress, has rarely been tested directly. Our research will utilize two models of chronic stress, which produce quite different forms of pituitary-adrenal dysregulation. The first model of chronic stress, repeated daily stress, has been widely used to understand how consequences of stressors can accumulate in time. We will use daily chair restraint, a physical and psychological stressor to which monkeys behaviorally adapt, but continue to elicit a substantial pituitary-adrenal response. Pilot data suggest that this type of repeated stress lead to chronic elevation of basal cortisol level. The second stressor-social instability--capitalizes on a broad-based understanding of the social interactions of monkeys and the evidence that alterations in the social situations of these monkeys provides naturalistic models of chronic stress. In contrast to the assumptions regarding the effects of physical stressors, social instability has been shown to produce long-term reductions in basal cortisol. Comparison of the two models of inducing chronic stress affords a unique opportunity to ask whether chronic stress subsumes multiple distinct syndromes, each associated with its own symptoms and risks. Future Directions We will begin detailed comparison of cognitive performance (using computer-assisted behavioral testing) and immunological competence in animals with chronically elevated or reduced glucocorticoids. Plans also include comparison of hippocampal structure and function in animals that have been subjected to chronic stress. KEY WORDS stress, cortisol, pituitary, adrenal FUNDING NIH Grant RR00169