Department of Psychiatry & Behavioral Neuroscience, University of Chicago 5841 S, Maryland Avenue (MC-3077), Chicago, IL, 60637, USA.
Neuropsychopharmacology. 2022 Oct;47(11):1892-1900. doi: 10.1038/s41386-022-01340-2. Epub 2022 Jun 14.
Models of addiction are based on neurobiological, behavioral, and pharmacological studies in animals, but translational support from human studies is limited. Studies are lacking in examining acute responses to alcohol in drinkers with alcohol use disorder (AUD), particularly in terms of relevant intoxicating doses and measurement of stimulating and rewarding effects throughout the breath alcohol concentration (BrAC) time curve. Participants were N = 60 AUD drinkers enrolled in the Chicago Social Drinking Project and examined in three random-order and blinded sessions for subjective and physiological responses to a beverage containing 0.0 g/kg, 0.8 g/kg, and 1.2 g/kg alcohol. BrAC in the alcohol sessions at 60 min was 0.09 g/dL and 0.13 g/dL, respectively. Both doses of alcohol produced significant biphasic effects on subjective measures of stimulation, euphoria, reward (liking and wanting), sedation, and neuroendocrine and cardiovascular factors. Increased pleasurable effects of alcohol were pronounced during the rising limb-to-peak BrAC and sedating effects emerged during the declining limb. Alcohol dose-dependently increased feel drug ratings and rewarding effects at peak BrAC or early declining limb, and physiological responses at the rising limb. Thus, rather than the notion of an overall tolerance, results show an alcohol response phenotype characterized by sensitivity to alcohol's stimulating, rewarding and physiological effects. The results of this study may aid in the conceptualization of alcohol addiction as a disorder characterized by the persistence of enhanced hedonic alcohol responses rather than chronic tolerance and reward deficiency.
成瘾模型基于动物的神经生物学、行为学和药理学研究，但来自人类研究的转化支持有限。在患有酒精使用障碍（AUD）的饮酒者中，缺乏研究来检查对酒精的急性反应，特别是在相关致醉剂量和测量整个呼气酒精浓度（BrAC）时间曲线中的刺激和奖励效应方面。参与者为 N = 60 名 AUD 饮酒者，他们参加了芝加哥社交饮酒项目，并在三个随机顺序和盲法会议中接受了含有 0.0 g/kg、0.8 g/kg 和 1.2 g/kg 酒精的饮料对主观和生理反应的检查。酒精会议中的 BrAC 在 60 分钟时分别为 0.09 g/dL 和 0.13 g/dL。两种剂量的酒精都对刺激、欣快、奖励（喜欢和想要）、镇静以及神经内分泌和心血管因素的主观测量产生了显著的双相效应。在 BrAC 上升到峰值期间，酒精的愉悦效果更加明显，而在下降期间则出现镇静作用。酒精剂量依赖性地增加了在 BrAC 峰值或早期下降支上的感觉药物评分和奖励效应，以及在上升支上的生理反应。因此，结果表明，酒精反应表型的特征是对酒精的刺激、奖励和生理效应敏感，而不是总体耐受，而不是整体耐受的概念。本研究的结果可能有助于将酒精成瘾概念化为一种以增强的愉快酒精反应持续存在而不是慢性耐受和奖励不足为特征的障碍。
