Genetic Analysis of Stress Response on EtOH Sensitivity

描述（由申请人提供）：心理压力对社会有着惊人的影响，在酗酒中起着重要作用。本研究的目的是探讨ILS和ISS小鼠暴露于应激和随后对乙醇敏感性之间关系的机制基础。我推测，乙醇敏感性的压力的影响是依赖于个人的遗传背景，这些遗传差异与个体差异的边缘-下丘脑-垂体-肾上腺轴（LHPA）激活。为了研究酒精和应激之间复杂的相互作用，我将利用乙醇敏感性表型，包括乙醇诱导的翻正反射丧失，低体温和低剂量激活。通过测量皮质酮和促肾上腺皮质激素水平以及下丘脑室旁核中相关基因表达的原位杂交，评估LHPA活性的外周和中枢成分。对小鼠暴露于酒精和压力后细胞活性发生变化的神经区域和通路的表征将进一步为人类群体的研究提供信息，以建立人类酒精中毒的预测因子，并最终开发出更有效的治疗方法。

DESCRIPTION (provided by applicant): Psychological stress has a staggering impact on society and plays a major role in alcoholism. The goal of the present study is to explore the mechanistic basis of the relationship between exposure to stress and subsequent sensitivity to ethanol in ILS and ISS mice. I hypothesize that the effects of stress on ethanol sensitivity are dependent on the genetic background of the individual, and that these genetic differences are related to individual differences in limbic-hypothalamic-pituitary-adrenal axis (LHPA) activation. To study the complex interactions between alcohol and stress, I will utilize ethanol sensitivity phenotypes including ethanol induced -loss of righting reflex, -hypothermia, and -low dose activation. Peripheral and central components of LHPA activity will be assessed by measurement of corticosterone and adrenocorticotropic hormone levels, and in situ hybridization of related gene expression in the paraventricular nucleus of the hypothalamus. The characterization of neural regions and pathways in which cellular activity is changed after exposure to alcohol and stress in mice will further inform studies in human populations to establish predictors of alcoholism in humans and ultimately develop more effective treatments.