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Human and animal studies recently questioned the use of the racemic drug in patients since a potential important role of the different enantiomers has been revealed with an efficacy thought to reside with the active R(+)\u2010enantiomer. Here we conducted experiments in the postdependent rat model of alcohol dependence to compare the efficacy of R(+)\u2010Baclofen or S(\u2212)\u2010Baclofen to that of RS(\u00b1)\u2010Baclofen on ethanol intake, seeking, and relapse. R(+)\u2010Baclofen was more effective than RS(\u00b1)\u2010Baclofen in reducing ethanol intake and seeking during acute withdrawal and during relapse after abstinence. We also used an original population approach in order to identify drug responders. We found a significant proportion of responders to S(\u2212)\u2010Baclofen and RS(\u00b1)\u2010Baclofen, displaying an increase in ethanol intake, and this increasing effect on alcohol intake was not seen in the R(+)\u2010Baclofen group. At an intermediate dose of R(+)\u2010Baclofen, devoid of any motor side effects, we identified a very large proportion of responders (75%) with a large decrease in ethanol intake (90% decrease). Finally, the response to RS(\u00b1)\u2010Baclofen on ethanol intake was correlated to plasma level of Baclofen. R(+)\u2010Baclofen and RS(\u00b1)\u2010Baclofen were effective in reducing sucrose intake. Our study has important clinical implication since it suggests that the wide variability in the therapeutic responses of patients to RS(\u00b1)\u2010Baclofen may come from the sensitivity to the R(+)\u2010Baclofen but also to the one of the S(\u2212)\u2010Baclofen that can promote an increase in ethanol intake.<\/jats:p>","DOI":"10.1111\/adb.12892","type":"journal-article","created":{"date-parts":[[2020,3,8]],"date-time":"2020-03-08T23:08:07Z","timestamp":1583708887000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Is R(+)\u2010Baclofen the best option for the future of Baclofen in alcohol dependence pharmacotherapy? Insights from the preclinical side"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9059-3513","authenticated-orcid":false,"given":"Victor","family":"Echeverry\u2010Alzate","sequence":"first","affiliation":[{"name":"INSERM UMR 1247\u2010Research Group on Alcohol and Pharmacodependences (GRAP) Universit\u00e9 de Picardie Jules Verne  Amiens France"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA) Hospital Regional Universitario de M\u00e1laga  Spain"},{"name":"Department of Psychobiology &amp; Behavioral Sciences Methods, School of Psychology Complutense University of Madrid  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0353-2777","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Jeanblanc","sequence":"additional","affiliation":[{"name":"INSERM UMR 1247\u2010Research Group on Alcohol and Pharmacodependences (GRAP) Universit\u00e9 de Picardie Jules 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