STRESS INDUCED INCREASES IN ALCOHOL EFFECTS

本申请提出了三个研究，探讨应激在介导酒精的积极强化效应中的作用。酒精的积极强化部分是由中脑边缘多巴胺系统提供的。皮质类固醇（cort）是在压力状态下和饮酒后释放的应激激素，已被证明可以调节多巴胺的激活。阻断皮质激素合成可能通过破坏积极强化和欣快感的主观体验，导致酒精和其他滥用药物的自我管理减少。为了在人类身上验证这一假设，提出了三项研究：1)研究1，每种情况下有23名受试者，将酒精/安慰剂与休克/无休克交叉使用，以确定皮质醇释放是否具有加性，并确定其对自我报告的快感的影响；2)研究2将使用美泰拉酮阻断皮质醇来研究HPA激活在酒精、压力反应中的作用及其相互作用。

This application proposes three studies that investigate the role of the stress in mediating alcohol's positive reinforcement effects. Alcohol's positive reinforcement is partly provided by the mesolimbic dopamine system. Corticosteroids (cort), stress hormones released during conditions of stress and after alcohol use, have been shown to moderate dopamine activation. A blockade of cort synthesis leads to decreased self administration of alcohol and other drugs of abuse, perhaps by disrupting the positive reinforcement and subjective experience of euphoria. To test this hypothesis in humans, three studies are proposed: 1) Study 1, with 23 subjects per condition, will cross alcohol/placebo with shock/no shock to determine if cortisol release is additive and to establish its effects on self- reported euphoria; and, 2) Study 2 will use a blockade of cortisol by Metyrapone to investigate the role of HPA activation in response to alcohol, stress and their interaction.