Behavioural sensitization to alcohol: Bridging the gap between preclinical research and human models

Abstract Alcohol use disorder (AUD) is an increasingly prevalent disorder that contributes significantly to the global burden of disease. According to the incentive sensitization theory (IST) of addiction, repeated alcohol exposure produces persistent neuroadaptations that promote the craving, relapse, and drug-taking characteristic of addiction. Critical to the IST model is the prediction that stimulant or hedonic drug effects become more pronounced with repeated exposure (i.e., sensitization). While there is an extensive body of preclinical alcohol sensitization research, there have been few studies examining this aspect of the incentive sensitization model in human alcohol research. In particular, developmental studies assessing sensitization over time in humans are lacking, due largely to ethical considerations precluding alcohol administration in alcohol-naive individuals, and the lack of a reliable protocol for the prospective measurement of sensitization. The lack of translation between preclinical and human models of alcohol sensitization presents a significant barrier to further understanding the relevance of IST to the development and progression of AUD. The present review discusses how the gap between preclinical and clinical alcohol sensitization research can be bridged and how animal studies can inform human alcohol sensitization research.