the-motivation-for-alcohol-reward-predictors-progressive-ratio

The Motivation for Alcohol Reward: Predictors of Progressive-Ratio Intravenous Alcohol Self-Administration in Humans

The Progressive Ratio (PR) self-administration paradigm is a common pre-clinical method used to examine the motivation for a drug attributed to a craving, ...

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The orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol.

The Leu72Met Polymorphism of the Prepro-ghrelin Gene is Associated With Alcohol Consumption and Subjective Responses to Alcohol: Preliminary Findings.

Impaired control over drinking is a significant marker of alcohol use disorder (AUD), and a potential target of intervention (Heather, Tebbutt, Mattick, & Zamir, 1993; Leeman, Toll, Taylor, & Volpicelli, 2009). Impaired control may be related to, but conceptually distinct from, impulsivity (Leeman, Patock-Peckham, & Potenza, 2012; Leeman, Ralevski, et al., 2014). However, the relationship between impaired control, impulsivity, and alcohol consumption, particularly in nondependent drinkers is less clear. This study aimed to characterize these relationships using a free-access intravenous alcohol self-administration (IV-ASA) paradigm in nondependent drinkers (N = 48). Results showed individuals with higher self-reported impaired control achieved higher blood alcohol concentrations (BAC) during the IV-ASA session and reported greater hedonic subjective responses to alcohol. Higher impaired control was also associated with greater positive urgency and reward sensitivity. Moderated-mediation analysis showed that the relationship between positive urgency and peak BAC was mediated by impaired control, and partially moderated by subjective alcohol response. These findings highlight the critical role of impaired control over drinking on alcohol consumption and subjective responses in nondependent drinkers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The relationship between impaired control, impulsivity, and alcohol self-administration in nondependent drinkers.

: Cluster of differentiation 38 (CD38) is a transmembrane protein expressed in dopaminergic reward pathways in the brain, including the nucleus accumbens (NAc). The GG genotype of a common single nucleotide polymorphism (SNP) within , rs3796863, is associated with increased social reward.: Examine whether  rs3796863 and  knockout (KO) are associated with reward-related neural and behavioral phenotypes.: Data from four independent human studies were used to test whether rs3796863 genotype is associated with: (1) intravenous alcohol self-administration (n = 64, 30 females), (2) alcohol-stimulated dopamine (DA) release measured using C-raclopride positron emission tomography (n = 22 men), (3) ventral striatum (VS) response to positive feedback measured using a card guessing functional magnetic resonance imaging (fMRI) paradigm (n = 531, 276 females), and (4) resting state functional connectivity (rsfc) of the VS (n = 51, 26 females). In a fifth study, we used a mouse model to examine whether  knockout influences stimulated DA release in the NAc core and dorsal striatum using fast-scanning cyclic voltammetry.: Relative to T allele carriers, G homozygotes at rs3796863 within  were characterized by greater alcohol self-administration, alcohol-stimulated dopamine release, VS response to positive feedback, and rsfc between the VS and anterior cingulate cortex. High-frequency stimulation reduced DA release among  KO mice had reduced dopamine release in the NAc.: Converging evidence suggests that  rs3796863 genotype may increase DA-related reward response and alcohol consumption.

A role for the  rs3796863 polymorphism in alcohol and monetary reward: evidence from CD38 knockout mice and alcohol self-administration, [11C]-raclopride binding, and functional MRI in humans.

Interindividual variation in responses to alcohol is substantial, posing challenges for medical management and for understanding the biological underpinnings of alcohol use disorders (AUD). It is important to understand whether diverse alcohol responses such as sedation, which is predictive of risk and partly heritable, occur concurrently or independently from responses such as blackouts and withdrawal. We hypothesized that latent factors accounting for sources of variance in diverse alcohol response phenotypes could be identified in a large, deeply phenotyped sample of patients with AUD.

Bethany L. Stangl

Human Psychopharmacology Laboratory,
Division of Intramural Clinical and Biological Research,
Human Psychopharmacology Laboratory, Division of Intramural Clinical and Biological Research

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The Motivation for Alcohol Reward: Predictors of Progressive-Ratio Intravenous Alcohol Self-Administration in Humans

Bethany L. Stangl

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NIAAA

The Motivation for Alcohol Reward: Predictors of Progressive-Ratio Intravenous Alcohol Self-Administration in Humans

Human Psychopharmacology Laboratory,
Division of Intramural Clinical and Biological Research,
Human Psychopharmacology Laboratory, Division of Intramural Clinical and Biological Research