Examining the predictive validity of alcohol-seeking following punishment-imposed abstinence in mice.

BACKGROUND: A defining feature of alcohol use disorder that has captured the attention of fundamental researchers is "persistent use despite negative consequences." The last two decades have seen the preclinical field adopt the use of punishment to model the adverse consequences associated with alcohol use. However, existing research has focused on rats as the model of choice and alcohol consumption as the prevailing outcome measure. Additionally, the predictive validity of these models, that is, testing currently approved FDA treatments, is yet to be realized. METHODS: Here, we examined punishment-imposed abstinence in mice using foot shock and measured reinstatement of alcohol-seeking following exposure to alcohol-associated cues and environmental contexts. RESULTS: We showed that mice voluntarily abstain from alcohol use when it is paired with a foot shock. Alcohol-associated cues and environmental contexts produced reinstatement of alcohol-seeking behavior. Finally, the predictive validity of our model was tested using naltrexone and varenicline, two medications to treat alcohol use disorder. Both naltrexone and varenicline reduced reinstatement of alcohol-seeking in male and female mice. CONCLUSIONS: Together, these data suggest that mice can display reinstatement of alcohol-seeking behavior following voluntary abstinence, and this model could be used to identify new medications for relapse prevention induced by environmental cues and contexts.