ALCOHOL AND STRESS--INTERACTIVE EFFECTS

酒精和压力——交互作用

• 批准号: 2044116
• 负责人: JOANNE WEINBERG
• 金额: $ 13.44万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2044116
• 关键词: ALCOHOL; STRESS; INTERACTIVE; EFFECTS

This research will systematically document changes in stress responsiveness induced by ethanol exposure, either in utero or in adulthood, and will investigate mechanisms that might mediate these changes. 1. Fetal alcohol exposure (FAE). Our working hypothesis is that pituitary-adrenal hyperresponsiveness and deficits in recovery following stress which have been observed in FAE animals result from ethanol-induced deficits in feedback control of the hypothalamo-pituitary-adrenal (HPA) axis. HPA function in FAE animals will be explored at multiple levels: 1) by both challenging and inhibiting the system, and 2) by examining hormonal responsiveness in parallel experiments both in vivo and in vitro. The role of hippocampal glucocorticoid receptors in mediating increased stress responsiveness of FAE animals will be studied by examining receptor occupancy under conditions of varying hormone levels, receptor plasticity (up-regulation following adrenalectomy [ADX]), and receptor down-regulation (during chronic stress or chronic corticoid administration). Possible deficits in feedback regulation at other levels of the HPA axis (hypothalamus, pituitary) will also be assessed. Sex differences in response will be examined in all studies. 2.Adult chronic alcoholism. Our working hypothesis is that chronic alcohol consumption, which consistently elevates basal corticoid levels in both animals and humans, will result in HPA hyperresponsiveness to stress. Chronic alcoholic males and females will be tested using acute and chronic stressors to determine HPA activation and recovery, and to examine HPA responsiveness both in vivo and in vitro. The role of hippocampal glucocorticoid receptors in mediating changes in stress responsiveness will be studied by examining receptor occupancy following acute and chronic stress and receptor plasticity (up-regulation following ADX). Possible deficits in feedback regulation at other levels of the HPA axis will also be examined. The ability to respond to stress is an important basic adaptive mechanism. Hyperresponsiveness or deficits in recovery following stress could have adverse physiological and behavioral consequences and thus impact negatively on health. The proposed research will have relevance to our understanding of sex differences in ethanol's effects, both in utero and in adulthood, on the adaptive function of the organism.

这项研究将系统地记录压力的变化 乙醇暴露诱导的反应性，无论是在子宫内还是在 成年，并将调查可能介导这些的机制， 变化 1. 胎儿酒精暴露（FAE）。 我们的假设是 垂体-肾上腺高反应性和恢复缺陷 在FAE动物中观察到的应激是由乙醇诱导的 下丘脑-垂体-肾上腺（HPA）反馈控制缺陷 轴线 将在多个水平探索FAE动物中的HPA功能：1） 通过挑战和抑制系统，和2）通过检查激素 在体内和体外的平行实验中， 的作用 海马糖皮质激素受体介导应激增加 FAE动物的反应性将通过检查受体 不同激素水平、受体可塑性条件下的占据 （肾上腺切除术后上调[ADX]）和受体下调 （在慢性应激或慢性皮质激素施用期间）。 可能 HPA轴其他水平的反馈调节缺陷 （下丘脑，垂体）也将进行评估。 的性别差异 将在所有研究中检查反应。 2.成人慢性酒精中毒。 我们的工作假设是， 饮酒，持续升高基础皮质激素水平， 动物和人类，将导致HPA对压力的高反应性。 慢性酗酒男性和女性将使用急性和慢性酒精测试 应激源，以确定HPA激活和恢复，并检查HPA 在体内和体外的反应性。 海马的作用 糖皮质激素受体介导应激反应的变化， 通过检查急性和慢性 应激和受体可塑性（ADX后上调）。 可能 HPA轴其他水平的反馈调节缺陷也将 接受检查。 对压力的反应能力是一种重要的基本适应能力 机制 应激后的高反应性或恢复缺陷 可能会产生不良的生理和行为后果， 对健康产生负面影响。 拟议的研究将与以下方面有关： 我们对乙醇影响的性别差异的理解， 在成年期，对机体的适应功能也有影响。