Translational underpinnings of motivation for alcohol in humans

摘要 尽管对酒精使用障碍（AUD）神经生物学的理解有了重大进展，但仍存在一个 这些见解转化为临床应用的差距。AUD的转化研究由以下方面促进： 使用实验操作和可以跨物种研究的理论结构。朝向 为了推进AUD的转化研究，PI完成了一个探索/开发项目，标题为： “在人类实验室中模拟酒精奖励和强化”（R21 AA 022752）。目的是 开发并测试人类饮酒动机的翻译任务。为此，我们将酒精 渐进式比率自我管理方法的挑战。静脉注射酒精 使用计算机辅助乙醇自注入（CASE）系统。在BrAC = 0.06 g/dl时，参与者 完成了一个渐进的比例自我管理任务，在这个任务中，他们被允许工作， 酒精含量按比例递增酒精自我管理任务捕捉动机， 酒精和镜像临床前的方法，理想的翻译假设的测试。除了 建模方法的“结果方面”的发展，“预测方面”包括AUD 现象学已经发展到临床翻译。成瘾神经临床评估（ANA） 建议将AUD现象学解析为三个领域，即激励显着性、负面情绪性， 和执行功能障碍我们的研究小组最近提供了一个独立的复制ANA 在1,679名重度饮酒者的样本中，连同成果评估方面的创新（即， 在人类中，ANA框架可以告知AUD进展的分期 因此，人类饮酒的动机提供了理想的行为科学结果。拟议 R 01应用程序建立在我们实验室开发翻译任务的大量工作基础上 人类饮酒动机的研究它通过测试ANA的三个维度来测试它们对 酒精动机在AUD患者中

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.