Individual differences in behavioral flexibility predict future volitional ethanol consumption in mice.

Cognitive control is key to regulating alcohol intake and preventing relapse. Behavioral inflexibility can prevent adaptive strategies such as mindfulness or other relapse-prevention behaviors. In a mouse model we investigated whether individual variability in behavioral flexibility (using attentional set-shifting task; ASST) predicts future alcohol intake. Adult male and female C57BL/6J mice were subjected to ASST using a bowl-digging paradigm where mice identify a baited bowl based on compound odor and textural cues. This was completed prior to any alcohol exposure. Individual performance across mice varied within the group. We integrated several metrics, specifically ASST stage completed, trials to completion, and errors performed to produce an individual performance index measure of behavioral flexibility. Afterward, ASST mice were trained to drink ethanol (15%, v/v, 1 h/day) for 3-4 weeks until intake stabilized. Using this prospective approach, we identified an inverse relationship between behavioral flexibility and drinking-less-flexible mice had a propensity to consume more alcohol. Similar relationships have been identified previously in non-human primates and rats. Our results show that the relationship between alcohol and behavioral flexibility is a robust trait that is conserved across species and can be used in mice to study neural substrates underlying these behaviors.