Proactive Versus Reactive Control Strategies Differentially Mediate Alcohol Drinking in Wistar and P rats

Abstract

Problematic alcohol consumption is associated with deficits in decision-making, and alterations in prefrontal cortex neural activity likely contributes. We hypothesized that differences in cognitive control would be evident between male Wistar rats and a model for genetic risk for alcohol use disorder (alcohol-preferring P rats). Cognitive control can be split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus whereas reactive control elicits goal-directed behavior at the time of a stimulus. We hypothesized that Wistars would show proactive control over alcohol-seeking whereas P rats would show reactive control over alcohol-seeking. Neural ensembles were recorded from prefrontal cortex during an alcohol seeking task that utilized two session types. On congruent sessions the CS+ was on the same side as alcohol access. Incongruent sessions presented alcohol opposite the CS+. Wistars, but not P rats, exhibited an increase in incorrect approaches during incongruent sessions, suggesting that Wistars utilized the previously learned task-rule. This motivated the hypothesis that ensemble activity reflecting proactive control would be observable in Wistars but not P rats. While P rats showed differences in neural activity at times relevant for alcohol delivery, Wistars showed differences prior to approaching the sipper. These results support our hypothesis that Wistars are more likely to engage proactive cognitive-control strategies whereas P rats are more likely to engage reactive cognitive control strategies. Although P rats were bred to prefer alcohol, differences in cognitive control may reflect a sequela of behaviors that mirror those in humans at risk for an AUD. Significance StatementCognitive control refers to the set of executive functions necessary for goal-directed behavior. It is a major mediator of addictive behaviors and can be subdivided into proactive and reactive cognitive control. We observed behavioral and electrophysiological differences between outbred Wistar rats and the selectively bred Indiana alcohol-preferring P rat while they sought and consumed alcohol. These differences are best explained by reactive cognitive control in P rats and proactive in Wistar rats.