ALCOHOL AND STRESS: INTERACTIVE EFFECTS

酒精和压力：相互作用

• 批准号: 3111655
• 负责人: JOANNE WEINBERG
• 金额: $ 10.96万
• 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 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3111655
• 关键词: adrenalectomy; alcoholic beverage consumption; alcoholism /alcohol abuse; circadian rhythms; cold temperature; corticosteroid receptors; corticosterone; corticotropin releasing factor; dexamethasone; embryo /fetus drug adverse effect; environmental adaptation; ethanol; fetal alcohol syndrome; gender difference; glucocorticoids; hippocampus; hypothalamic pituitary axis; laboratory rat; mature animal; physiologic stressor; pituitary adrenal axis; prenatal stress; psychological stressor; receptor expression; spleen; statistics /biometry; stress; stressor; thymus; tissue /cell culture

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 乙醇暴露引起的反应，无论是在子宫内还是在体内 成年后，并将研究可能介导这些的机制 变化。 1. 胎儿酒精暴露（FAE）。 我们的工作假设是 垂体-肾上腺过度反应和术后恢复缺陷 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。 FAE 动物中的 HPA 功能将在多个层面上进行探索：1) 通过挑战和抑制系统，以及 2) 通过检查荷尔蒙 体内和体外平行实验的反应性。 角色 海马糖皮质激素受体介导应激增加的作用 FAE动物的反应性将通过检查受体来研究 不同激素水平、受体可塑性条件下的占有率 （肾上腺切除术 [ADX] 后上调）和受体下调 （在慢性压力或长期服用皮质类固醇期间）。 可能的 HPA 轴其他水平的反馈调节存在缺陷 （下丘脑、垂体）也将被评估。 性别差异 所有研究都将检验反应。 2.成人慢性酒精中毒。 我们的工作假设是慢性 饮酒，持续升高基础皮质激素水平 无论是动物还是人类，都会导致 HPA 对压力过度反应。 慢性酗酒的男性和女性将使用急性和慢性测试 确定 HPA 激活和恢复并检查 HPA 的压力源 体内和体外的反应性。 海马体的作用 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后的受体占用情况来研究 压力和受体可塑性（ADX 后上调）。 可能的 HPA 轴其他层面的反馈调节缺陷也会 被检查。 应对压力的能力是重要的基本适应能力 机制。 压力后反应过度或恢复不足 可能会产生不良的生理和行为后果，因此 对健康产生负面影响。 拟议的研究将与 我们对乙醇在子宫内的影响的性别差异的理解 在成年期，则影响机体的适应功能。