A SELECTIVE ROLE FOR THE LATERAL ORBITOFRONTAL CORTEX IN FLEXIBLE ALCOHOL-SEEKING BEHAVIOR​

Alcohol seeking and relapse are characterized by impaired behavioral flexibility and persistent responding despite changes in action–outcome contingencies, behaviors that have been linked to malfunction of the orbitofrontal cortex (OFC). Although the OFC has been implicated in various different aspects of alcohol seeking, including motivation and cue-driven relapse, it remains unclear whether OFC involvement reflects a general contribution to alcohol reward processing or a more selective role in adapting alcohol-seeking behavior under dynamic contingency demands.
We used chemogenetic inhibition of the lateral OFC (l-OFC) in male Long Evans to examine alcohol-seeking behavior in stable and flexible instrumental conditions. Rats were trained to self-administer alcohol in operant paradigm and were subsequently tested for motivation using a progressive ratio schedule and cue-induced reinstatement following extinction. Inhibition of l-OFC did not alter stable alcohol self-administration, motivation to obtain alcohol reward, or cue-induced reinstatement of alcohol seeking. These results suggest that l-OFC activity is not critically required for alcohol’s incentive value or for cue-maintained alcohol seeking in our animal model. In contrast, l-OFC inhibition significantly reduced alcohol-seeking responses in a within-session reward-block lever alternation task, in which the reinforced action switched repeatedly after fixed numbers of earned alcohol deliveries without explicit cues signaling the change. Thus, our results suggest that dysfunction in the l-OFC promotes maladaptive alcohol use by impairing the ability to flexibly control alcohol-seeking actions. Next we are investigating whether ventral OFC activity contributes differently to alcohol seeking and behavioral flexibility.