Corticosteroid Dependent Mechanisms of Stress Adaptation

皮质类固醇依赖性压力适应机制

基本信息

批准号：
6922784
负责人：
ROBERT L SPENCER
金额：
$ 19.49万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-01 至 2006-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6922784
关键词：
arginine vasopressin behavioral /social science research tag behavioral habituation /sensitization corticosteroid receptors corticosterone corticotropin releasing factor hippocampus hormone regulation /control mechanism hypothalamic pituitary adrenal axis immunocytochemistry laboratory rat mineralocorticoids paraventricular nucleus psychological stressor psychosomatic disorders receptor expression restraint stress

项目摘要

Stress triggers not only an immediate response from specialized stress response systems, but triggers adaptive processes that are manifest by an altered magnitude of subsequent stress responses. Thus, exposure to repeated stress often leads to either habituation or sensitization of stress responses. Although substantial progress has been made in understanding the immediate physiological response to stress, as well as some of the physiological consequences of repeated stress, very little progress has been made in understanding the adaptive processes that contribute to stress response habituation or sensitization. These adaptive processes, however, may be crucial in determining the long-term physiological and psychological consequences of stress. Some psychological disorders may be directly, related to the development of sensitized stress responses (e.g. post- traumatic stress disorder) or to the impaired development of stress response habituation (e.g. depression). Previous studies have found in rats that the expression of hypothalamic-pituitary- adrenal (HPA) axis stress-response habituation is dependent on corticosteroid hormone activity in the brain mediated by mineralocorticoid receptors (MR). The proposed project will further study mechanisms by which corticosterone regulates stress habituation. The specific aims are: (1) to determine the anatomical site(s) responsible for MR antagonist modulation of HPA axis stress habituation, (2) to determine whether the expression of HPA axis stress habituation and its blockade by MR antagonist treatment is associated with changes in corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) gene expression in the paraventricular nucleus of the hypothalamus (PVH), (3) to determine whether HPA axis stress habituation is associated with a generalized shift in HPA axis dependence on MR- media corticosteroid negative feedback, and (4) to determine whether HPA axis stress habituation is associated with a change in MR or glucocorticoid receptor (GR) expression in the rat brain.

压力不仅会触发专门的压力反应系统的立即反应，还会触发适应性过程，该过程通过随后的压力反应幅度的改变来体现。因此，反复承受压力通常会导致压力反应的习惯化或敏感化。尽管在理解对压力的直接生理反应以及重复压力的一些生理后果方面已经取得了实质性进展，但在理解有助于压力反应习惯化或敏感化的适应性过程方面却进展甚微。然而，这些适应过程对于确定压力的长期生理和心理后果可能至关重要。一些心理障碍可能与敏感应激反应（例如创伤后应激障碍）的发展或应激反应习惯的发展受损（例如抑郁症）直接相关。先前的研究在大鼠中发现，下丘脑-垂体-肾上腺（HPA）轴应激反应习惯的表达依赖于盐皮质激素受体（MR）介导的大脑中皮质类固醇激素的活性。拟议的项目将进一步研究皮质酮调节压力习惯的机制。具体目标是：（1）确定负责 MR 拮抗剂调节 HPA 轴应激习惯的解剖部位，（2）确定 HPA 轴应激习惯的表达及其通过 MR 拮抗剂治疗的阻断是否与下丘脑室旁核 (PVH) 中促肾上腺皮质激素释放激素 (CRH) 和精氨酸加压素 (AVP) 基因表达的变化，(3) 以确定 HPA 轴应激习惯是否存在与 HPA 轴对 MR 介质皮质类固醇负反馈的依赖性的普遍变化相关，以及 (4) 确定 HPA 轴应激习惯是否与大鼠大脑中 MR 或糖皮质激素受体 (GR) 表达的变化相关。