Department of Psychology, Indiana University-Purdue University, Indianapolis, Indiana, USA.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Addict Biol. 2021 Nov;26(6):e13016. doi: 10.1111/adb.13016. Epub 2021 Feb 5.
Preclinical models of alcohol use disorder (AUD) have advanced theoretical, mechanistic, and pharmacological study of the human condition. "Liking" and "wanting" behaviors reflect core processes underlying several models of AUD. However, the development and application of translational models of these preclinical approaches are at an incipient stage. The goal of this study was to examine how intravenous free-access and progressive-ratio, operant-response human alcohol self-administration paradigms can be used as translational human model parallels of preclinical "liking" and "wanting." Participants were 40 adults (mean age = 23.7, SD = 2.0; 45% female) of European descent who reported 12.6 drinking days (SD = 5.2) out of the previous 30 (average = 4.1 drinks per drinking day [SD = 1.7]). Individuals diverged in their alcohol self-administration behavior, such that free-access and progressive-ratio paradigm outcomes were not significantly correlated (p = 0.44). Free-access alcohol seeking was related to enjoying alcohol (p < 0.001), but not craving (p = 0.48), whereas progressive-ratio seeking at similar levels of alcohol exposure was related to craving (p = 0.02), but not enjoying (p = 0.30). Family history of alcoholism, venturesomeness traits, and disinhibition traits were unrelated (ps > 0.70) to preferred level of breath alcohol concentration (BrAC) in the free-access session, a measure of liking alcohol. Family history of alcoholism, disinhibition traits, and recent drinking history were significantly related (ps < 0.05) to alcohol seeking in the progressive-ratio paradigm, a measure of wanting alcohol. We conclude that intravenous alcohol self-administration paradigms show promise in modeling behaviors that characterize and parallel alcohol "liking" and "wanting" in preclinical models. These paradigms provide a translational link between preclinical methods and clinical trials.
酒精使用障碍(AUD)的临床前模型促进了人类状况的理论、机制和药理学研究。“喜欢”和“想要”行为反映了几种 AUD 模型的核心过程。然而,这些临床前方法的转化模型的开发和应用仍处于起步阶段。本研究的目的是检验静脉内自由接入和递增比率操作性反应人类酒精自我给药范式如何可作为临床前“喜欢”和“想要”的转化人类模型平行物。参与者为 40 名欧洲血统的成年人(平均年龄为 23.7,标准差为 2.0;45%为女性),他们在过去 30 天中有 12.6 天饮酒(标准差为 5.2;平均每天饮酒 4.1 杯[标准差为 1.7])。个体的酒精自我给药行为存在差异,因此自由接入和递增比率范式的结果没有显著相关性(p=0.44)。自由接入酒精寻求与享受酒精有关(p<0.001),但与渴望无关(p=0.48),而在相似的酒精暴露水平下进行递增比率寻求与渴望有关(p=0.02),但与享受无关(p=0.30)。酒精滥用家族史、冒险特质和抑制解除特质与自由接入期的首选呼气酒精浓度(BrAC)无关(p>0.70),这是衡量对酒精的喜爱程度的指标。酒精滥用家族史、抑制解除特质和近期饮酒史与递增比率范式中的酒精寻求显著相关(p<0.05),这是衡量对酒精的渴望程度的指标。我们得出结论,静脉内酒精自我给药范式在对临床前模型中酒精“喜欢”和“想要”的行为进行建模方面显示出了前景。这些范式为临床前方法和临床试验之间提供了转化联系。