ALCOHOL AND STRESS: INTERACTIVE EFFECTS

酒精和压力：相互作用

• 批准号: 3111659
• 负责人: JOANNE WEINBERG
• 金额: $ 12.33万
• 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/3111659
• 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 酒精暴露引起的反应性，无论是在宫内还是在 成年期，并将调查可能调解这些 改变。 1.胎儿酒精暴露(FAE)。我们的工作假设是 术后恢复中的垂体-肾上腺高反应性和缺陷 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 轴心。HPA在FAE动物中的作用将在多个水平上进行探索：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在介导应激增加中的作用 将通过检测受体来研究FAE动物的反应性 在不同激素水平、受体可塑性条件下的入住率 (肾上腺切除后上调[ADX])和受体下调 (在慢性应激或长期使用皮质激素期间)。可能的 HPA轴其他层面的反馈调节缺陷 (下丘脑、脑垂体)也将被评估。中国的性别差异 将在所有研究中检查反应。 2.成人慢性酒精中毒。我们的工作假设是慢性 饮酒，持续提高基础皮质醇水平 无论是动物还是人类，都会导致HPA对压力的高反应性。 慢性酒精中毒的男性和女性将使用急性和慢性 确定HPA激活和恢复的应激源，并检查HPA 体内和体外的响应性。海马区的作用 糖皮质激素受体在介导应激反应改变中的作用 通过检查急性和慢性之后的受体占有率来进行研究 应激和受体可塑性(ADX后上调)。可能的 在HPA轴的其他层面的反馈调节的缺陷也将 接受检查。 应对压力的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期缺陷 可能产生不良的生理和行为后果，因此 对健康产生负面影响。拟议的研究将与以下方面有关 我们对酒精影响的性别差异的理解，无论是在子宫内 以及成年后，对有机体的适应功能的影响。