Motivation for IV Alcohol Self-Administration in Humans

The goal of this translational study is to understand different reasons why people between the ages of 21 and 65 with alcohol use disorder are motivated to self-administer alcohol. The main questions it aims to answer are:

• How does a person's desire for a reward affect their motivation to self-administer alcohol?
• How does a person's emotions affect their motivation to self-administer alcohol?
• How does a person's cognitive functioning affect their motivation to self-administer alcohol?

Participants will be asked to complete questionnaires about their mood, habits, and functioning and will complete an IV alcohol administration that will include pressing a button to receive additional doses of IV alcohol.

This study combines alcohol challenge and progressive ratio self-administration methodologies to test the effects of each of the three dimensions of the Addictions Neuroclinical Assessment (ANA) on motivation for alcohol use. The experimental design consists of a translational study in which 210 individuals with current AUD (mild-to-severe) will complete an intravenous (IV) alcohol administration followed by a progressive ratio self-administration paradigm, where participants must press a button a number of times to receive an infusion of alcohol. All participants will be phenotyped for the three dimensions of the ANA, including incentive salience, negative emotionality, and executive dysfunction. For these models, the primary outcome in the progressive ratio self-administration paradigm will be: (a) breakpoint (i.e., the point in the progressive ratio model at which the participant stops button presses for alcohol) and (b) peak BrAC (i.e., the highest level of BrAC reached in the trial). At baseline and after the target BrAC of 0.06 g/dl in the alcohol challenge component of the paradigm, participants will report on (a) alcohol craving, (b) negative mood, and (c) loss of control over drinking. All participants will provide blood samples at baseline and at target BrAC =0.06 g/dl for analyses of the proposed exploratory biomarkers of HPA axis activation (ACTH, cortisol) and inflammation (IL-6, IL-10, TNF-α, CRP). The successful completion of this project will advance translational science of AUD by testing the ANA framework within a conceptually rich and valid translational task of motivation for alcohol in humans. Advanced data analytic methods (i.e., machine learning) and careful attention to AUD severity as a marker to AUD stage, will result in clinically useful findings that can inform AUD assessment, treatment, and biomarker development.