RESPONSES TO CHRONIC STRESS IN MONKEYS

慢性社会和心理压力源，普遍存在 在现代社会中，是健康和福利的重要决定因素。 这项研究调查了高度社会化的灵长类动物， 社会和环境的扰动， 并导致长时间的 垂体-肾上腺调节 目的本研究计划是 旨在评估认知、免疫和神经生物学 造成慢性升高和慢性 恒河猴的垂体-肾上腺活动减少。 结果 大部分的免疫学和神经生物学研究， 应激依赖于糖皮质激素药理学操作 程度. 这项研究的假设，这是压力引起的， 糖皮质激素升高导致健康风险相关 很少被直接测试。 我们的研究将 利用两种慢性压力模型， 垂体肾上腺失调的形式。 第一种慢性 压力，重复的日常压力，已被广泛用于了解如何 压力源的后果可以随着时间的推移而积累。 我们将每天使用 椅子约束，身体和心理的压力源， 猴子的行为适应，但继续引起大量的 垂体肾上腺反应 试验数据表明，这种类型的 反复应激导致基础皮质醇水平慢性升高。 第二个压力源-社会不稳定-利用了基础广泛的 了解猴子的社会互动和证据 这些猴子社会地位的改变 慢性压力的自然模型 与假设相反， 关于身体压力的影响，社会不稳定 已经被证明可以长期降低基础皮质醇水平。 比较两种慢性应激模型， 这是一个独特的机会， 不同的综合征，每一个都与自己的症状和风险有关。 未来方向我们将开始详细比较 性能（使用计算机辅助行为测试）和 在具有慢性升高或 减少糖皮质激素。 计划还包括比较海马 结构和功能的动物已经受到慢性 应力 关键词应激，皮质醇，垂体，肾上腺 格兰特RR 00169

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