A preclinical model for identifying rats at risk of alcohol use disorder

Alcohol use is one of the world's leading causes of death and disease, although only a small proportion of individuals develop persistent alcohol use disorder (AUD). The identification of vulnerable individuals prior to their chronic intoxication remains of highest importance. We propose here to adapt current methodologies for identifying rats at risk of losing control over alcohol intake by modeling diagnostic criteria for AUD: Inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Factor analysis showed that these three addiction criteria loaded on one underlying construct indicating that they represent a latent construct of addiction trait. Further, not only vulnerable rats displayed higher ethanol consumption, and higher preference for ethanol over sweetened solutions, but they also exhibited pre-existing higher anxiety as compared to resilient rats. In conclusion, the present preclinical model confirms that development of an addiction trait not only requires prolonged exposure to alcohol, but also depends on endophenotype like anxiety that predispose a minority of individuals to lose control over alcohol consumption.