Under the Influence: Effects of Ethanol Exposure and Anxiety on Motivation for Gambling-like Cues

Introduction: The frequent co-occurrence of gambling disorder with alcohol use and anxiety disorders has implicated shared underlying mechanisms between these disorders. Recent research suggests that reward uncertainty may powerfully enhance the incentive value of gambling cues. As such, when lights and sounds (CS) are repeatedly associated with unpredictable monetary rewards in a casino slot machine, they may trigger or maintain compulsive behaviors characteristic of gambling disorder. It remains unclear how alcohol use or anxiety in adolescence may confer high risk for gambling disorder by enhancing vulnerability to reward-related cues. Methods: Here, we studied the effects of adolescent ethanol exposure and anxiety on the desire for a cue (CS) associated with uncertain rewards (UCS). Prior to behavioral testing, male and female adolescent rats were given free access to ethanol or control jello for 20 days. After a 10-day withdrawal period, rats were then trained in an autoshaping task to associate lever (CS) presentations with the delivery of sucrose pellets (UCS) on either a certain or uncertain reward contingency. Cue attraction was measured by interaction with the lever (sign-tracking) and the sucrose delivery dish (goal-tracking) across sessions. After autoshaping, all groups were tested to assess whether the cue became a conditioned reinforcer, powerfully able to motivate behavior on its own. Animals were then subsequently trained under an omission contingency to evaluate the persistence of sign-tracking when lever pressing resulted in the omission of reward. Anxiety levels were also measured by scoring the time spent on the open arms of an elevated plus maze. Results: The results of the present study replicate previous findings that reward uncertainty may shape compulsive gambling behaviors by enhancing attraction and an attentional bias towards cues associated with uncertain reward. In addition, the results suggest that high anxiety individuals may be most vulnerable to the motivating effects of reward uncertainty. Ethanol exposure did not appear to enhance cue attraction beyond the effects seen under conditions of reward uncertainty. However, adolescent ethanol exposure was associated with increased anxiety, particularly in females and in animals with high voluntary ethanol intake during adolescence. There were notable gender differences in ethanol consumption, as females on average consumed significantly more ethanol. Discussion: Cues associated with uncertain rewards may take on incentive value and serve as powerful reinforcers of gambling behaviors. Chronic and heavy alcohol use may contribute to heightened anxiety levels, while high anxiety may contribute to overattribution of value to reward cues in gambling. The present study highlights specific mechanisms that may contribute to the frequent co-occurrence of high anxiety, heavy alcohol use, and vulnerability to problematic gambling in adolescence. Additionally, they provide specific avenues for further study to better understand the roles of anxiety, reward uncertainty, and alcohol use in the onset and maintenance of gambling disorder.