Aversion-resistant alcohol seeking in the human laboratory

Abstract

Background

Aversion-resistant, or “compulsive,” drinking is well-studied as a preclinical model of alcohol use disorder. Human studies have largely relied on subjective self-report of aversion-resistant drinking. The goal of this study was to develop and test a behavioral model of aversion-resistant alcohol seeking in the human laboratory, facilitating translational research on this important risk factor.

Methods

A sample of 84 adults aged 21–55 (mean age = 32.2 years, 54.8% female, 58.3% white) who endorsed heavy alcohol use (mean AUDIT = 11.3, SD = 5.6) completed an interview/screening session and two counterbalanced progressive-ratio intravenous alcohol self-administration sessions, one in which alcohol seeking was paired with aversive and the other neutral stimuli (each beginning with a 40-min alcohol prime of 60 mg/dL). Study hypotheses were preregistered at clinicaltrials.gov (Study Details—Human Alcohol Seeking Despite Aversion—ClinicalTrials.gov, ID NCT03648840).

Results

Contrary to hypotheses, across the whole sample, cumulative lifetime drinking did not relate specifically to aversion-resistant alcohol seeking; rather, those with more extensive drinking histories worked more for alcohol across both sessions. A parallel growth curve model analysis found that less of an alcohol-prime-associated increase in stimulation was related to more aversion-resistant alcohol seeking.

Conclusions

These data suggest that aversion-resistant alcohol seeking may stem from the blunted stimulating effects of alcohol, consistent with the low-level response theory driving excessive alcohol seeking, or from acquired tolerance from drinking. This human model of aversion-resistant alcohol seeking can be paired with preclinical models to explore and evaluate new clinical treatment targets.