Translational underpinnings of motivation for alcohol in humans

点击翻译按钮获取中文摘要

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.