Department of Psychology, University of California, Los Angeles, CA, USA.
Department of Psychology, Binghamton University, Binghamton, NY, USA.
Neuropsychopharmacology. 2018 Aug;43(9):1891-1899. doi: 10.1038/s41386-018-0086-9. Epub 2018 May 8.
The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in the motivational structure of alcohol drinking: from positive reinforcement in early-stage drinking to negative reinforcement in late-stage dependence. However, direct empirical support for this preclinical model from human experiments is limited. This study tests predictions derived from the Allostatic Model in humans. Specifically, this study tested whether alcohol use severity (1) independently predicts subjective responses to alcohol (SR; comprised of stimulation/hedonia, negative affect, sedation and craving domains), and alcohol self-administration and 2) moderates associations between domains of SR and alcohol self-administration. Heavy drinking participants ranging in severity of alcohol use and problems (N = 67) completed an intravenous alcohol administration paradigm combining an alcohol challenge (target BrAC = 60 mg%), with progressive ratio self-administration. Alcohol use severity was associated with greater baseline negative affect, sedation, and craving but did not predict changes in any SR domain during the alcohol challenge. Alcohol use severity also predicted greater self-administration. Craving during the alcohol challenge strongly predicted self-administration and sedation predicted lower self-administration. Neither stimulation, nor negative affect predicted self-administration. This study represents a novel approach to translating preclinical neuroscientific theories to the human laboratory. As expected, craving predicted self-administration and sedation was protective. Contrary to the predictions of the Allostatic Model, however, these results were inconsistent with a transition from positively to negatively reinforced alcohol consumption in severe AUD. Future studies that assess negative reinforcement in the context of an acute stressor are warranted.
应激适应模型提出，酒精使用障碍（AUD）与酒精摄入的动机结构转变有关：从早期饮酒的正强化转变为晚期依赖的负强化。然而，来自人类实验的对这一临床前模型的直接实证支持是有限的。本研究在人类中测试了应激适应模型的预测。具体来说，本研究检验了酒精使用严重程度（1）是否独立预测对酒精的主观反应（SR；包括刺激/欣快、负性情绪、镇静和渴望领域），以及酒精自我给药，（2）是否调节 SR 与酒精自我给药之间的关联。严重程度不同的大量饮酒参与者（N=67）完成了一项静脉内酒精给药范式，该范式结合了酒精挑战（目标 BrAC=60mg%）和递增比例自我给药。酒精使用严重程度与更大的基线负性情绪、镇静和渴望有关，但并不预测酒精挑战期间任何 SR 领域的变化。酒精使用严重程度也预测了更大的自我给药。酒精挑战期间的渴望强烈预测自我给药，而镇静预测自我给药减少。刺激和负性情绪均不能预测自我给药。本研究代表了将临床前神经科学理论转化为人类实验室的一种新方法。正如预期的那样，渴望预测了自我给药，而镇静则具有保护作用。然而，与应激适应模型的预测相反，这些结果与严重 AUD 中从正强化到负强化的酒精消费转变不一致。未来有必要在急性应激的背景下评估负强化的研究。
