Already moderate alcohol consumption has detrimental long-term effects on brain function. However, how alcohol produces its potent addictive effects despite being a weak reinforcer is a poorly understood conundrum that likely hampers the development of successful interventions to limit heavy drinking. In this translational study, we demonstrate widespread increased mean diffusivity in the brain gray matter of chronically drinking humans and rats. These alterations appear soon after drinking initiation in rats, persist into early abstinence in both species, and are associated with a robust decrease in extracellular space tortuosity explained by a microglial reaction. Mathematical modeling of the diffusivity changes unveils an increased spatial reach of extrasynaptically released transmitters like dopamine that may contribute to alcohol’s progressively enhanced addictive potency.

适度饮酒已经对大脑功能产生有害的长期影响。然而，尽管酒精是一种较弱的强化剂，但酒精如何产生其强大的成瘾作用是一个鲜为人知的难题，这可能会阻碍成功干预以限制大量饮酒的发展。在这项转化研究中，我们证明了长期饮酒的人和大鼠大脑灰质中的平均扩散率普遍增加。这些改变在大鼠开始饮酒后很快出现，在两个物种中持续到早期禁欲，并且与由小胶质细胞反应解释的细胞外空间曲折的强烈减少有关。