Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health & Science University and VA Medical Center, Portland, OR 97239, USA.
Addict Biol. 2010 Apr;15(2):125-44. doi: 10.1111/j.1369-1600.2009.00191.x.
If people are brought into the laboratory and given alcohol, there are pronounced differences among individuals in many responses to the drug. Some participants in alcohol challenge protocols show a cluster of 'low level of responses to alcohol' determined by observing post-drinking-related changes in subjective, motor and physiological effects at a given dose level. Those individuals characterized as having low level of response (LR) to alcohol have been shown to be at increased risk for a lifetime diagnosis of alcohol dependence (AD), and this relationship between low LR and AD appears to be in part genetic. LR to alcohol is an area where achieving greater consilience between the human and the rodent phenotypes would seem to be highly likely. However, despite extensive data from both human and rodent studies, few attempts have been made to evaluate the human and animal data systematically in order to understand which aspects of LR appear to be most directly comparable across species and thus the most promising for further study. We review four general aspects of LR that could be compared between humans and laboratory animals: (1) behavioral measures of subjective intoxication; (2) body sway; (3) endocrine responses; and (4) stimulant, autonomic and electrophysiological responses. None of these aspects of LR provide completely face-valid direct comparisons across species. Nevertheless, one of the most replicated findings in humans is the low subjective response, but, as it may reflect either aversively valenced and/or positively valenced responses to alcohol as usually assessed, it is unclear which rodent responses are analogous. Stimulated heart rate appears to be consistent in animal and human studies, although at-risk subjects appear to be more rather than less sensitive to alcohol using this measure. The hormone and electrophysiological data offer strong possibilities of understanding the neurobiological mechanisms, but the rodent data in particular are rather sparse and unsystematic. Therefore, we suggest that more effort is still needed to collect data using refined measures designed to be more directly comparable in humans and animals. Additionally, the genetically mediated mechanisms underlying this endophenotype need to be characterized further across species.
如果将人们带入实验室并给予酒精，那么在许多对药物的反应中，个体之间存在明显的差异。在酒精挑战方案中，一些参与者表现出一系列“低水平的酒精反应”，通过观察在给定剂量水平下饮酒后相关的主观、运动和生理效应的变化来确定。那些被认为对酒精反应水平低（LR）的个体被发现患终身酒精依赖（AD）的风险增加，而这种低 LR 与 AD 之间的关系似乎部分是遗传的。LR 对酒精是一个在人类和啮齿动物表型之间实现更大一致性的领域。然而，尽管有来自人类和啮齿动物研究的广泛数据，但很少有人试图系统地评估人类和动物数据，以了解哪些方面的 LR 在物种之间最直接可比，因此最有希望进一步研究。我们回顾了可以在人类和实验室动物之间进行比较的 LR 的四个一般方面：（1）主观醉酒的行为测量；（2）身体摇晃；（3）内分泌反应；（4）兴奋剂、自主和电生理反应。LR 的这些方面都没有提供完全有效的跨物种直接比较。然而，在人类中最具重复性的发现之一是低主观反应，但由于它可能反映了对酒精的厌恶和/或积极评估，因此尚不清楚哪种啮齿动物反应与之相似。刺激心率在动物和人类研究中似乎是一致的，尽管使用这种测量方法，处于风险中的受试者对酒精似乎更敏感而不是不敏感。激素和电生理数据提供了理解神经生物学机制的强有力可能性，但啮齿动物数据特别稀疏且缺乏系统性。因此，我们建议仍然需要更多的努力来收集使用更直接可比的人类和动物精细测量设计的数据。此外，需要进一步在物种之间表征这种内表型的遗传介导机制。
