Tolerance to baclofen’s sedative effect in alcohol addicted patients: no dissipation after a period of abstinence

We read with great interest the recent report by Besheer et al. (2004) about the effects of GABA B receptor agonists on parameters of alcohol self-administration in ethanol-naive and self-administering mice. Confirming previous preclinical studies (Colombo et al. 2000,2002), the authors showed that baclofen was able to decrease alcohol intake in pretreated animals, reducing ethanol-reinforced responding at doses that did not alter water-reinforced responding. Moreover, the authors showed that ethanol-experienced mice were less sensitive to the sedative properties of baclofen than naive mice, suggesting that the combination of baclofen and alcohol or baclofen alone would have less of a negative impact on alcoholic patients than on naive drinker subjects; this observation underlines further the safety of the drug in the treatment of alcohol addiction. However, the authors claim to show evidence for the permanence of cross-tolerance to the agonist after a period of alcohol abstinence, although no data are at present available. Our clinical experience, correctly quoted by the authors (Addolorato et al.2000,2002a), are in line with the data by Besheer et al. (2004)