Baclofen-induced reduction of alcohol reinforcement in alcohol-preferring rats

Recent studies have demonstrated that treatment with the GABAB receptor agonist, baclofen, reduces alcohol intake in selectively bred Sardinian alcohol-preferring (sP) rats tested under the homecage 2-bottle "alcohol vs water" choice regimen. The present study was designed to investigate whether baclofen also reduces alcohol reinforcing effects in sP rats. To this aim, sP rats were trained to lever-press for oral alcohol (15%, v/v) or sucrose (0.3%, w/v; included as alternative reinforcer to evaluate the specificity of baclofen effect on alcohol reinforcement) under a fixed ratio schedule of 4. Once steady levels of alcohol or sucrose self-administration behavior were established, the effect of acutely administered baclofen (0, 1.7 and 3 mg/kg, i.p.) and naloxone (0, 1 and 3 mg/kg, i.p.; included as reference compound) on alcohol- or sucrose-reinforced responding was evaluated. Baclofen administration dose-dependently, although not specifically, reduced alcohol-reinforced responding to an extent comparable to that of naloxone. Baclofen also produced a dose-dependent and specific delay in the onset of alcohol-reinforced responding, suggesting that it suppressed the rats' motivation to start drinking alcohol. These data are discussed in terms of adding further support to the hypothesized involvement of the GABAB receptor in the neural system mediating alcohol reinforcement. These data are also in agreement with the results of recent preliminary clinical studies suggesting that baclofen may have therapeutic efficacy in the treatment of alcohol dependence.