Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, USA.
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA.
Neuropsychopharmacology. 2021 Jul;46(8):1421-1431. doi: 10.1038/s41386-021-00993-9. Epub 2021 Mar 16.
Individuals who abuse alcohol often show exaggerated attentional bias (AB) towards alcohol-related cues, which is thought to reflect reward conditioning processes. Rodent studies indicate that dopaminergic pathways play a key role in conditioned responses to reward- and alcohol-associated cues. However, investigation of the dopaminergic circuitry mediating this process in humans remains limited. We hypothesized that depletion of central dopamine levels in adult alcohol drinkers would attenuate AB and that these effects would be mediated by altered function in frontolimbic circuitry. Thirty-four male participants (22-38 years, including both social and heavy drinkers) underwent a two-session, placebo-controlled, double-blind dopamine precursor depletion procedure. At each visit, participants consumed either a balanced amino acid (control) beverage or an amino acid beverage lacking dopamine precursors (order counterbalanced), underwent resting-state fMRI, and completed behavioral testing on three AB tasks: an alcohol dot-probe task, an alcohol attentional blink task, and a task measuring AB to a reward-conditioned cue. Dopamine depletion significantly diminished AB in each behavioral task, with larger effects among subjects reporting higher levels of binge drinking. The depletion procedure significantly decreased resting-state functional connectivity among ventral tegmental area, striatum, amygdala, and prefrontal regions. Beverage-related AB decreases were mediated by decreases in functional connectivity between the fronto-insular cortex and striatum and, for alcohol AB only, between anterior cingulate cortex and amygdala. The results support a substantial role for dopamine in AB, and suggest specific dopamine-modulated functional connections between frontal, limbic, striatal, and brainstem regions mediate general reward AB versus alcohol AB.
个体在滥用酒精时，往往会对与酒精相关的线索表现出夸张的注意力偏差（AB），这被认为反映了奖励条件作用过程。啮齿动物研究表明，多巴胺能通路在对与奖励和酒精相关的线索的条件反应中起着关键作用。然而，人类中介导这一过程的多巴胺能回路的研究仍然有限。我们假设，成年饮酒者的中枢多巴胺水平耗竭会减弱 AB，而这些影响将通过额眶皮质回路功能的改变来介导。34 名男性参与者（22-38 岁，包括社交饮酒者和重度饮酒者）接受了两次、安慰剂对照、双盲多巴胺前体耗竭程序。在每次访问中，参与者都饮用了一种平衡的氨基酸（对照）饮料或一种缺乏多巴胺前体的氨基酸饮料（顺序平衡），进行了静息状态 fMRI 扫描，并在三个 AB 任务上完成了行为测试：酒精点探测任务、酒精注意力眨眼任务和奖励条件线索的 AB 任务。多巴胺耗竭显著降低了每个行为任务中的 AB，在报告 binge 饮酒水平较高的受试者中，效果更大。该耗竭程序显著降低了腹侧被盖区、纹状体、杏仁核和前额叶区域之间的静息状态功能连接。饮料相关的 AB 减少与额岛皮层和纹状体之间以及仅在酒精 AB 中与前扣带回皮层和杏仁核之间的功能连接减少有关。结果支持多巴胺在 AB 中的重要作用，并表明额叶、边缘、纹状体和脑干区域之间的特定多巴胺调节功能连接介导了一般奖励 AB 与酒精 AB。
