Alcohol Cue-Induced Ventral Striatum Activity Predicts Subsequent Alcohol Self-Administration

Abstract

Background: Human laboratory paradigms are a pillar in medication development for alcohol use disorders (AUD). Neuroimaging paradigms, in which individuals are exposed to cues that elicit neural correlates of alcohol craving (e.g., mesocorticolimbic activation), are increasingly utilized to test the effects of AUD medications. Elucidation of the translational effects of these neuroimaging paradigms on human laboratory paradigms, such as self-administration, is warranted. The current study is a secondary analysis examining whether alcohol cue-induced activation in the ventral striatum is predictive of subsequent alcohol self-administration in the laboratory.

Methods: Non-treatment-seeking heavy drinkers of East Asian descent (n = 41) completed a randomized, placebo-controlled, double-blind, crossover experiment on the effects of naltrexone on neuroimaging and human laboratory paradigms. Participants completed 5 days of study medication (or placebo); on day 4, they completed a neuroimaging alcohol taste cue-reactivity task. On the following day (day 5), participants completed a 60-minute alcohol self-administration paradigm.

Results: Multilevel Cox regressions indicated a significant effect of taste cue-elicited ventral striatum activation on latency to first drink, Wald χ² = 2.88, p = 0.05, such that those with higher ventral striatum activation exhibited shorter latencies to consume their first drink. Similarly, ventral striatum activation was positively associated with total number of drinks consumed, F(1, 38) = 5.90, p = 0.02. These effects were significant after controlling for alcohol use severity, OPRM1 genotype, and medication. Other potential regions of interest (anterior cingulate, thalamus) were not predictive of self-administration outcomes.

Conclusions: Neuroimaging alcohol taste cue paradigms may be predictive of laboratory paradigms such as self-administration. Elucidation of the relationships among different paradigms will inform how these paradigms may be used synergistically in experimental medicine and medication development.

Keywords: Alcohol Self-administration; Cue-Induced Craving; Human Laboratory; Neuroimaging; Ventral Striatum.

Figure 1.

CONSORT Diagram *The scanner utilized for the study was upgraded towards the end of the study. Due to parameter compatibility concerns, scanning data was not collected from 12 MRI-eligible participants.

Figure 2.

Anatomical region of interest mask for ventral striatum (left and right: 108 and 86 voxels, respectively). ROI extracted from the Harvard Oxford atlas thresholded at 25% based on the maximum probability labels. MNI coordinates for depicted slices are X=2 (left), Y=8 (middle), Z=−6 (right). L=Left, R=right, S=superior, I=inferior, A=anterior, P=posterior.

Figure 3.

Multilevel cox regressions depicting the relationship between alcohol-elicited ventral striatum activation and subsequent latency to first drink (seconds), controlling for medication, OPRM1, and Timeline Follow-Back drinks per drinking day. Ventral striatum median-split activation (SA_VSmed; 0 = below median, 1 = above median) is for visualization purposes only.