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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA010760-24
Application #
9614842
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
24
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Xu, Ting; Falchier, Arnaud; Sullivan, Elinor L et al. (2018) Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo. Cell Rep 23:429-441
Iancu, Ovidiu D; Colville, Alexander; Walter, Nicole A R et al. (2018) On the relationships in rhesus macaques between chronic ethanol consumption and the brain transcriptome. Addict Biol 23:196-205
Morales, Angelica M; Jones, Scott A; Ehlers, Alissa et al. (2018) Ventral striatal response during decision making involving risk and reward is associated with future binge drinking in adolescents. Neuropsychopharmacology 43:1884-1890
Gavin, David P; Hashimoto, Joel G; Lazar, Nathan H et al. (2018) Stable Histone Methylation Changes at Proteoglycan Network Genes Following Ethanol Exposure. Front Genet 9:346
Purohit, Kush; Parekh, Puja K; Kern, Joseph et al. (2018) Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice. Alcohol Clin Exp Res 42:879-888
Müller-Oehring, Eva M; Kwon, Dongjin; Nagel, Bonnie J et al. (2018) Influences of Age, Sex, and Moderate Alcohol Drinking on the Intrinsic Functional Architecture of Adolescent Brains. Cereb Cortex 28:1049-1063
Iancu, Ovidiu Dan; Colville, Alex M; Wilmot, Beth et al. (2018) Gender-Specific Effects of Selection for Drinking in the Dark on the Network Roles of Coding and Noncoding RNAs. Alcohol Clin Exp Res :
Kafkafi, Neri; Agassi, Joseph; Chesler, Elissa J et al. (2018) Reproducibility and replicability of rodent phenotyping in preclinical studies. Neurosci Biobehav Rev 87:218-232
Qiu, J; Wagner, E J; Rønnekleiv, O K et al. (2018) Insulin and leptin excite anorexigenic pro-opiomelanocortin neurones via activation of TRPC5 channels. J Neuroendocrinol 30:
Allen, Daicia C; Ford, Matthew M; Grant, Kathleen A (2018) Cross-Species Translational Findings in the Discriminative Stimulus Effects of Ethanol. Curr Top Behav Neurosci 39:95-111

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