Translational underpinnings of motivation for alcohol in humans

人类饮酒动机的转化基础

• 批准号: 10345709
• 负责人: LARA A. RAY
• 金额: $ 41.93万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10345709
• 关键词: 3-Dimensional; Alcoholic beverage heavy drinker; Alcohols; Attention; Basic Science; Behavior; Behavioral Sciences; Biological Markers; Blood Tests; Blood specimen; Clinical; Clinical Sciences; Collection; Computer Assisted; Corticotropin; Data Analytics; Data Set; Development; Dimensions; Disease Progression; Emotional; Ethanol; Executive Dysfunction; Growth; Human; Hydrocortisone; Impairment; Individual; Inflammation; Infusion procedures; Interleukin-10; Interleukin-6; Laboratories; Longterm Follow-up; Machine Learning; Methodology; Modeling; Motivation; Neurobiology; Outcome; Outcome Assessment; Participant; Patient Self-Report; Peripheral; Phenotype; Protocols documentation; Reporting; Research; Rewards; Role; Sampling; Schedule; Self Administration; Severities; Side; Staging; System; TNF gene; Testing; Translational Research; Translations; Work; addiction; alcohol craving; alcohol reinforcement; alcohol reward; alcohol seeking behavior; alcohol use disorder; analytical method; biomarker development; blood-based biomarker; breath alcohol measurement; clinical application; clinical translation; craving; discounting; disease classification; drinking; hypothalamic-pituitary-adrenal axis; incentive salience; innovation; insight; intravenous administration; machine learning model; negative mood; phenomenological models; pre-clinical; pre-clinical research; preference; response; therapy development

ABSTRACT Despite significant advances in the understanding of the neurobiology of alcohol use disorder (AUD), there is a gap in the translation of these insights into clinical applications. Translational research in AUD is facilitated by the use of experimental manipulations and theoretical constructs that can be studied across species. Towards advancing translational research in AUD, the PI completed an Exploratory/Developmental Project entitled: “Modeling alcohol reward and reinforcement in the human laboratory” (R21 AA022752). The objective was to develop and test a translational task of motivation for alcohol in humans. To do so, we combined alcohol challenge with progressive ratio self-administration methodologies. Alcohol was administered intravenously using the Computer-Assisted Self-Infusion of Ethanol (CASE) system. At BrAC = 0.06 g/dl, participants completed a progressive ratio self-administration task in which they were allowed to work to be infused more alcohol following a progressive ratio schedule. The alcohol self-administration task captures motivation for alcohol and mirrors preclinical methodologies, ideal for testing of translational hypotheses. In addition to developments in the “outcome side” of the modeling approach, the “predictor side” comprised of AUD phenomenology has progressed towards clinical translation. The Addiction Neuroclinical Assessment (ANA) proposed to parse AUD phenomenology into three domains, namely incentive salience, negative emotionality, and executive dysfunction. Our research group has recently provided an independent replication of the ANA framework in a sample of 1,679 heavy drinkers. Together with the innovation in outcome assessment (i.e., progressive ratio self-administration in humans), the ANA framework can inform staging of AUD progression and as such, motivation for alcohol in humans provides an ideal behavioral science outcome. The proposed R01 application builds upon the extensive work from our laboratory on the development of a translational task for drinking motivation in humans. It does so by testing the three dimensions of the ANA for their effects on alcohol motivation in individuals with AUD.

抽象的 尽管对酒精使用障碍（AUD）的神经生物学的理解取得了重大进展，但仍然存在 将这些见解转化为临床应用的差距。澳元的转化研究得到了促进 使用可以跨物种研究的实验操作和理论结构。向 为了推进 AUD 的转化研究，PI 完成了一个探索性/开发项目，题为： “在人类实验室中模拟酒精奖励和强化”（R21 AA022752）。目标是 开发并测试人类酒精动机的转化任务。为此，我们将酒精混合在一起 挑战渐进比例自我管理方法。酒精被静脉注射 使用计算机辅助乙醇自我注入（CASE）系统。当 BrAC = 0.06 g/dl 时，参与者 完成了一项渐进比例自我管理任务，其中允许他们工作以获得更多输液 酒精遵循渐进比例表。酒精自我管理任务捕捉了动机 酒精和镜像临床前方法，非常适合测试转化假设。此外 建模方法“结果端”的发展，即由澳元组成的“预测端” 现象学已经向临床转化方向发展。成瘾神经临床评估 (ANA) 提出将 AUD 现象学解析为三个领域，即激励显着性、消极情绪、 和执行功能障碍。我们的研究小组最近提供了 ANA 的独立复制 该框架以 1,679 名酗酒者为样本。连同结果评估的创新（即 人类自行给药的渐进比例），ANA 框架可以为 AUD 进展的分期提供信息 因此，人类饮酒的动机提供了理想的行为科学结果。拟议的 R01 应用程序建立在我们实验室在开发翻译任务方面的广泛工作的基础上 人类的饮酒动机。它通过测试 ANA 的三个维度对 澳元个体的饮酒动机。