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Abstract
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BACKGROUND: Alcohol stimulates cerebral blood flow (CBF) in brain reward regions, but neural processes that support sustained alcohol motivation after the first drink are not well understood.
METHODS: Using a novel placebo-controlled, randomized, crossover experiment, 27 alcohol users who binge drink (BD; 15 M, 12 F) and 25 social drinkers (SD; 15 M, 10 F) who do not binge, engaged in a behavioral test of self-motivated alcohol consumption to assess initial alcohol motivation using an Alcohol Taste Test (ATT) conducted with alcoholic and non-alcoholic placebo beer on separate days immediately prior to perfusion functional magnetic resonance imaging (fMRI) scanning. Immediately following each fMRI scan, participants also engaged in a post-scan ATT with placebo beer on both days to assess sustained alcohol self-motivation without active alcohol effects and relative to initial alcohol self-motivation. Linear mixed-effects models were used to examine the effects of drinking group on the placebo-controlled effect of initial alcohol motivation on brain perfusion (whole brain corrected p<0.001, cluster corrected p<0.025) and on the relationship between placebo-controlled brain perfusion and sustained alcohol motivation.
RESULTS: Initial alcohol self-motivation in the alcohol relative to placebo session led to markedly decreased activation in the medial orbitofrontal cortex (OFC) and the ventral striatum, indicative of neural reward tolerance, but also enhanced neural response in behavioral intention regions of the supplementary motor area (SMA) and inferior frontal gyrus (IFG) regions in the BD relative to SD group. Moreover, greater sustained alcohol motivation was seen in BD relative to SD in the post-scan ATT in the alcohol relative to placebo session. Correspondingly, only in BD and only in the alcohol session, lower alcohol-induced OFC response correlated with concurrent sensitized SMA response, and each predicted the subsequent sustained higher alcohol motivation in the post-scan ATT.
CONCLUSIONS: The findings suggest that alcohol-related OFC tolerance plays a significant role in sustained alcohol motivation, and that both specific alcohol-related neural reward tolerance and pre-motor sensitization responses may contribute to escalating alcohol motivation to drive excessive alcohol intake, even prior to development of alcohol use disorders.
Language: en |