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

Abstract : 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. (C) 2018 Elsevier Ltd. All rights reserved.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03589628
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Soumis le : vendredi 25 février 2022 - 17:10:50
Dernière modification le : samedi 26 février 2022 - 03:00:16

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Maria Carmen Gonzalez-Marin, Sophie Lebourgeois, Jerome Jeanblanc, Momar Diouf, Mickaël Naassïla. Evaluation of alcohol use disorders pharmacotherapies in a new preclinical model of binge drinking. NEUROPHARMACOLOGY, 2018, 140, pp.14-24. ⟨10.1016/j.neuropharm.2018.07.015⟩. ⟨hal-03589628⟩

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