Alcohol use disorder (AUD) is a complex, chronic, relapsing disorder with multiple interacting genetic and environmental influences. Numerous studies have verified the influence of genetics on AUD, yet the underlying biological pathways remain unknown. One strategy to interrogate complex diseases is the use of endophenotypes, which deconstruct current diagnostic categories into component traits that may be more amenable to genetic research. In this review, we explore how an endophenotype such as sensitivity to alcohol can be used in conjunction with rodent models to provide mechanistic insights into AUD. We evaluate three alcohol sensitivity endophenotypes (stimulation, intoxication, and aversion) for their translatability across human and rodent research by examining the underlying neurobiology and its relationship to consumption and AUD. We show examples in which results gleaned from rodents are successfully integrated with information from human studies to gain insight in the genetic underpinnings of AUD and AUD-related endophenotypes. Finally, we identify areas for future translational research that could greatly expand our knowledge of the biological and molecular aspects of the transition to AUD with the broad hope of finding better ways to treat this devastating disorder.

中文翻译：

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酒精敏感性作为酒精使用障碍的内表型：探索其在啮齿动物和人类之间的转化效用


酒精使用障碍 (AUD) 是一种复杂、慢性、复发性疾病，受多种相互作用的遗传和环境影响。大量研究已经证实了遗传学对 AUD 的影响，但潜在的生物学途径仍然未知。研究复杂疾病的一种策略是使用内表型，它将当前的诊断类别解构为可能更适合基因研究的组成特征。在这篇综述中，我们探讨了如何将内表型（例如对酒精的敏感性）与啮齿动物模型结合使用，以提供对 AUD 的机制见解。我们通过检查潜在的神经生物学及其与消费和 AUD 的关系，评估了三种酒精敏感性内表型（刺激、中毒和厌恶）在人类和啮齿动物研究中的可转化性。我们展示了一些例子，其中从啮齿动物收集的结果成功地与人类研究的信息相结合，以深入了解 AUD 和 AUD 相关内表型的遗传基础。最后，我们确定了未来转化研究的领域，这些领域可以极大地扩展我们对向 AUD 过渡的生物学和分子方面的了解，并有望找到更好的方法来治疗这种破坏性疾病。