Prior Chronic Alcohol Exposure Enhances Pavlovian-to-Instrumental Transfer

Alcohol dependence is associated with aberrant decision-making processes, particularly in the presence of alcohol-related environmental cues. For instance, alcohol cues can trigger alcohol seeking, consumption, and even relapse behavior. Recently, works have suggested that alcohol dependence may induce more general alterations in cued processes that support adaptive behavior, including enhanced cue control of volitional behavior unrelated to alcohol use. Here we examine this hypothesis by combining prior exposure to chronic intermittent ethanol and repeated withdrawal (CIE) procedures with a Pavlovian-to-instrumental transfer (PIT) task in mice. The PIT task entails training a Pavlovian association, separately training an instrumental contingency, and a final test during which the Pavlovian cue and instrumental action are combined for the first time. We first tested two variants of the PIT procedure in ethanol-naive mice, differing in part in the duration of Pavlovian conditioned cues (short or long). We found in the PIT test that the short cue procedure produced negative transfer, whereas the long cue procedure produced positive transfer. We then used the long cue variant to examine PIT behavior in mice previously exposed to either CIE or air vapor. We found that prior CIE exposure strengthened PIT behavior, with enhanced instrumental responding during presentation of the food-associated cue. We further found that this enhancement in CIE mice persisted even after devaluation of the food outcome. Our findings suggest that ethanol dependence can enhance the influence of reward-predictive cues on ongoing behavior. Greater non-alcohol cue control of behavior may reflect the effect of chronic ethanol exposure on neural circuitry critical for cue-guided behavior in general.