Having a family history of alcohol use disorder (AUD) increases one's likelihood of developing an AUD. The mechanisms underlying this risk are unclear, but familial AUD-related premorbid differences in brain circuitry have been demonstrated. Further, studies comparing the subjective responses to alcohol in family history- positive and family-history negative (FH+/FH-) individuals indicate that FH+ individuals report more stimulation and less sedation than FH- individuals, and these effects are seen across the ascending and descending limbs of the blood alcohol curve (BAC), respectively. These subjective phenotypes are associated with the perpetuation of alcohol use. However, little is known about concurrent alterations in brain circuitry across the BAC and the extent to which these alterations, and differing subjective effects, reflect underlying neurobiological differences in AUD risk. Accordingly, we aim to address this knowledge gap using functional magnetic resonance imaging techniques. We will compare patterns of functional connectivity in FH+ and FH- individuals, matched for drinking history, across the BAC during acute alcohol intoxication. Specifically, functional connectivity magnetic resonance imaging (fcMRI) will be examined in relation to the BAC, using a 90-min scanning protocol in a total of 72 young adults (36 FH+/36 FH-; age 21; groups matched for prior drinking history). Twenty minutes prior to beverage consumption, a pre-beverage assessment will occur and an intravenous (IV) line will be placed to allow repeated blood draws. Next, participants will consume a beverage (0 [placebo], 0.6 g/kg [total alcohol dose]; order counterbalanced between sessions for a within subjects dosing design) and scanning will begin, including 70 minutes of fcMRI across the BAC. Every 10 minutes throughout the fcMRI data collection (at the same times blood samples are taken), subjects will also complete a brief subjective effects questionnaire, so that subjective effects (stimulation, sedation) can be recorded and related to fcMRI between specific brain regions. Comparing functional connectivity underlying response to acute alcohol intake across the BAC in the brains of at-risk, compared to lower risk, individuals will provide useful information about the neurobiology of alcohol's actions and interactive factors associated with abuse liability (subjective response), which may ultimately inform intervention efforts.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Comprehensive Center (P60)
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Special Emphasis Panel (ZAA1)
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Oregon Health and Science University
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