Abstract

Alcohol use disorder (AUD) is characterized by impairments in decision-making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision-making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre-existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce. Here, we found that cognitive flexibility was impaired in rodents selectively bred for excessive alcohol consumption (alcohol preferring (P) rats), on the attentional set-shifting task (ASST). Further, the degree of impairment is predictive of future ethanol consumption, thus suggesting that cognitive inflexibility is a stable trait capable of predisposing one for drinking. In a second set of experiments, we observed an impairment in the ability of P rats to use a previously learned rule to guide foraging in a simple discrimination task. Convergence across several behavioral measures suggested that this impairment reflected a state of heightened urgency that interfered with decision-making. A similar impairment on a simple discrimination task was observed in Wistar rats with a history of alcohol consumption. These findings indicate how trait and state variables-in this case, impaired cognitive flexibility and heightened urgency, respectively-may influence the risk for excessive drinking. Furthermore, our results suggest that cognitive inflexibility and urgency can exist as both risk factors for and the result of alcohol exposure.

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