Different Effects of Alcohol Exposure on Action and Outcome-Related Orbitofrontal Cortex Activity

Alcohol dependence can result in long-lasting deficits to decision-making and action control. Neurobiological investigations have identified orbitofrontal cortex (OFC) as important for outcome-related contributions to goal-directed actions during decision-making. Prior work has shown that alcohol dependence induces long-lasting changes to OFC function that persist into protracted withdrawal and disrupts goal-directed control over actions. However, it is unclear whether these changes in function alter representation of action and outcome-related neural activity in OFC. Here, we used the well-validated chronic intermittent ethanol (CIE) exposure and withdrawal procedure to model alcohol dependence in mice and performed in vivo extracellular recordings during an instrumental task in which lever-press actions made for a food outcome. We found alcohol dependence disrupted goal-directed action control and increased OFC activity associated with lever-pressing but decreased OFC activity during outcome-related epochs. The ability to decode outcome-related information, but not action information, from OFC activity following CIE exposure was reduced. Hence, chronic alcohol exposure induced a long-lasting disruption to OFC function such that activity associated with actions was enhanced, but OFC activity contributions to outcome-related information was diminished. This has important implications for hypotheses regarding compulsive and habitual phenotypes observed in addiction.