Garrison A C S, Wu W, Cox M R, Haines D, Hays J, Mlungwana M K, Kosobud A E K, Kareken D A, O'Connor S, Plawecki M H, Cyders M A
Department of Psychology, Indiana University Indianapolis, Indianapolis, Indiana, USA.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Alcohol Clin Exp Res (Hoboken). 2025 Jul 6. doi: 10.1111/acer.70078.
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.
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).
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.
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.
抗厌恶或“强迫性”饮酒作为酒精使用障碍的临床前模型已得到充分研究。人体研究在很大程度上依赖于对抗厌恶饮酒的主观自我报告。本研究的目的是在人体实验室中开发并测试一种抗厌恶酒精寻求行为模型，以促进对这一重要风险因素的转化研究。
84名年龄在21 - 55岁之间的成年人（平均年龄 = 32.2岁，54.8%为女性，58.3%为白人），他们认可大量饮酒（平均酒精使用障碍识别测试 [AUDIT] 评分为11.3，标准差 = 5.6），完成了一次访谈/筛查环节以及两次平衡的渐进比率静脉注射酒精自我给药环节，其中一次酒精寻求与厌恶刺激配对，另一次与中性刺激配对（每次均从40分钟的60毫克/分升酒精初始剂量开始）。研究假设已在clinicaltrials.gov上预先注册（研究详情 - 尽管厌恶仍寻求酒精 - ClinicalTrials.gov，标识符NCT03648840）。
与假设相反，在整个样本中，累积终生饮酒量与抗厌恶酒精寻求并无特定关联；相反，饮酒史更长的人在两个环节中为获取酒精付出的努力更多。平行增长曲线模型分析发现，与酒精初始剂量相关的刺激增加越少，与更多的抗厌恶酒精寻求相关。
这些数据表明，抗厌恶酒精寻求可能源于酒精刺激作用减弱，这与驱动过度酒精寻求的低水平反应理论一致，或者源于饮酒产生的后天耐受性。这种抗厌恶酒精寻求的人体模型可与临床前模型相结合，以探索和评估新的临床治疗靶点。
