Aversion-resistant alcohol seeking in the human laboratory.

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.