Repeated cocaine exposure dysregulates cognitive control over cue-evoked reward-seeking behavior during Pavlovian-to-instrumental transfer.

Drug-paired cues acquire powerful motivational properties, but only lead to active drug-seeking behavior if they are potent enough to overwhelm the cognitive control processes that serve to suppress such urges. Studies using the Pavlovian-to-instrumental transfer (PIT) task have shown that rats pretreated with cocaine or amphetamine exhibit heightened levels of cue-motivated food-seeking behavior, suggesting that exposure to these drugs sensitizes the incentive motivational system. However, the PIT testing protocol can also create conflict between two competing behavioral responses to the reward-paired cue: active reward seeking (e.g., lever pressing) and passive conditioned food-cup approach behavior. We therefore investigated whether repeated cocaine exposure alters the way in which rats use cue-based reward expectations to resolve such conflict. In-depth analysis of previously published and new research confirmed that when drug-naïve rats are given a cue that signals the timing of a delayed noncontingent reward, they adaptively transition from reward seeking to conditioned approach behavior, facilitating efficient collection of the predicted reward. In contrast, cocaine-exposed rats exhibit pronounced behavioral dysregulation, increasing, rather than suppressing, their reward-seeking behavior over time, disrupting their ability to passively collect reward. Such findings speak to the important and sometimes overlooked role that cognitive control plays in determining the motivational impact of cues associated with drug and nondrug rewards.