Disrupted decision making in adult male rats after prolonged withdrawal from ethanol vapor exposure.

Background: Chronic alcohol use disrupts decision making and cognitive flexibility, but its long-term effects after adult exposure remain poorly understood. While prior studies have shown moderate disruptions in behavioral flexibility weeks after ethanol (EtOH) withdrawal, we tested whether such deficits persist after prolonged abstinence (>6 months) in male rats.

Methods: Male rats underwent 4 weeks of EtOH vapor or air exposure starting at postnatal day 75. After approximately 7 months of withdrawal, rats (postnatal day ~300) completed a series of reversal learning tasks featuring distinct reward probabilities with deterministic (100/0%) and uncertain (90/10% and 80/20%) schedules. We assessed win-stay and lose-shift behaviors, as well as response latencies. Reinforcement learning (RL) models were fit hierarchically to identify group differences in value updating during reward-guided decision making.

Results: When rats had novel reversal experience under deterministic conditions, ethanol (EtOH)-exposed rats showed increased lose-shift behavior in trials preceding the reversal point. When a moderate outcome uncertainty (90/10) was introduced, EtOH rats displayed reduced win-stay behavior in trials after reversal when learning new contingencies. With continued training under greater outcome uncertainty (80/20), these changes were not manifested. Furthermore, RL models revealed that rats employed distinct learning processes depending on the reward schedule. Across all RL models, EtOH-exposed rats exhibited a consistently high decay of unchosen action values, either through faster forgetting or enhanced updating after negative outcomes.

Conclusions: These findings demonstrate that a remote history of adult alcohol exposure can lead to persistent, uncertainty-sensitive disruptions in reward-based decision making, even after exceptionally long withdrawal.