Evaluation of alcohol use disorders pharmacotherapies in a new preclinical model of binge drinking.

Binge drinking is defined as a pattern of drinking leading to intoxication in a single short session and is a serious but preventable public health problem. Only few animal models of voluntary binge drinking using an operant paradigm are available in outbred animals and in general they do not display good face validity. We recently set up a new model of binge drinking behavior using an operant self-administration paradigm in which rats drink to intoxication level in 15-min daily session. Here we tested the current pharmacotherapies of alcohol use disorder: Acamprosate, (R)-Baclofen, gamma-hydroxybutyric acid, Nalmefene and Naltrexone. Our results show that all drugs are effective in reducing ethanol drinking. All drugs except Acamprosate also reduced the motivational properties of ethanol (breakpoint). (R)-Baclofen and gamma-hydroxybutyric acid were effective on ethanol intake at doses devoid of side effects. Among the tested drugs only (R)-Baclofen, gamma-hydroxybutyric acid and Naltrexone reduced reacquisition after a period of abstinence. Interestingly, the efficacy of all drugs except Nalmefene to reduce ethanol drinking was slightly and positively correlated with the basal level of drinking thus revealing heavy drinking as a predictive factor. In summary, all current alcohol use disorder pharmacotherapies were effective in our model of binge drinking behavior thus bringing new data regarding its good predictive validity. The tested drugs display some specificity regarding their effect on motivation, reacquisition and also in terms of individual factors such as basal drinking level. Our new model opens promising perspectives about the development of pharmacotherapies targeting binge drinking behavior.