Translational dynamics of alcohol tolerance of preclinical models and human laboratory studies

Increasing sensitivity due to alcohol intake has been explored using molecular and cellular mechanisms of sensitization and adaptive biobehavioral changes as well as through negative experiences of altered function during withdrawal. However, within both a preclinical and human laboratory setting, little has been elucidated toward understanding the neural substrates of decreased sensitivity to alcohol effects, that is, alcohol tolerance. More paradigms assessing alcohol tolerance are needed. Tolerance can be assessed through both self-reported response (subjective) and observed (objective) measurements. Therefore, sensitivity to alcohol is an exploitable variable that can be utilized to disentangle the diverse alcohol use disorder (AUD) phenotypical profile. This literature review focuses on preclinical models and human laboratory studies to evaluate alcohol tolerance and its modulating factors. Increased understanding of alcohol tolerance has the potential to reduce gaps between preclinical models and human laboratory studies to better evaluate the development of alcohol-related biobehavioral responses. Furthermore, alcohol tolerance can be used as an AUD phenotypic variable in randomized clinical trials designed for developing AUD therapies.