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.

摘要 尽管在了解酒精使用障碍(AUD)的神经生物学方面取得了重大进展，但仍有 在将这些见解转化为临床应用方面存在差距。澳大利亚的翻译研究通过以下方式得到促进 使用可以跨物种研究的实验操作和理论构造。朝向 为了推进澳元的翻译研究，国际翻译协会完成了一个探索性/发展项目，题为： 《人体实验室酒精奖励与强化模型》(R21 AA022752)。我们的目标是 开发并测试一项人类饮酒动机的翻译任务。为了做到这一点，我们将酒精 挑战渐进式比率自我管理方法。酒精是通过静脉注射的 使用计算机辅助乙醇自我输注(CASE)系统。在brc=0.06g/dl时，参与者 完成了累进比例的自我管理任务，允许他们工作以获得更多 酒精按照递进比例时间表。酒精自我管理任务捕捉到了 酒精和镜像临床前方法学，非常适合测试翻译假说。除了……之外 在建模方法的“结果方面”方面的发展，“预测方面”由澳元组成 现象学已经向临床翻译迈进。成瘾神经临床评估(ANA) 提出将AUD现象学解析为三个领域，即激励显著、消极情绪、 和执行功能障碍。我们的研究小组最近提供了一个独立的ANA复制品 对1,679名酗酒者进行了抽样调查。与成果评估的创新(即， 人类自我给药的进展率)，ANA框架可以为AUD进展提供信息 因此，人类饮酒的动机提供了一个理想的行为科学结果。建议数 R01应用程序建立在我们实验室开发翻译任务的广泛工作基础上 对人类饮酒动机的影响。它通过测试ANA的三个维度来测试它们对 AUD患者的酒精动机。