INTRODUCTION

Alcohol & Alcoholism Vol. 37, No. 5, p. 477, 2002 INTRODUCTION GIANCARLO COLOMBO and GIAN LUIGI GESSA Department of Neuroscience ‘Bernard B. Brodie’, University of Cagliari, Cittadella Universitaria, S. S. 554, Monserrato (CA) I-09042, Italy In recent years, accumulating lines of evidence have suggested that the γ-aminobutyric acid (GABA)B receptor agonists, and particularly baclofen, may reduce the reinforcing properties of drugs of dependence (specifically cocaine, heroin, nicotine and alcohol), limiting their self-administration in laboratory animals and, in the few clinical studies conducted to date, their use by human addicts. The interest in this promising pharmacotherapeutic strategy in the addiction field led us to focus on baclofen and the GABAB receptor a symposium at the 8th Congress of ESBRA, held in Paris on 15–18 September 2001. The present issue of Alcohol and Alcoholism includes the Proceedings of the above symposium. Actually, this journal issue restores the initial symposium programme, including the contributions of those North American colleagues who could not attend the ESBRA Congress because of the tragic events of 11 September 2001 in New York and Washington, DC. David Roberts and his colleagues have made a great effort to investigate the effects of baclofen on cocaine self-administration in rats. Their paper (Brebner et al.; pp. 478–482) extensively reviews the results of their studies, which feature the rather unique profile of the suppressing properties of baclofen on cocaine reinforcement. Their paper also contains an interesting extension to humans, with the results of a recent positron emission tomography study on the ability of baclofen to prevent limbic activation associated with cue-induced craving for cocaine in cocaine addicts. Baclofen has also been shown to suppress the intravenous self-administration of heroin in rats. The paper by Xi and Stein (pp. 483–492) reviews these data and also provides evidence for the ability of baclofen to suppress heroin-stimulated release of dopamine in the rat nucleus accumbens. These data support the hypothesis that baclofen may exert its reducing effect on heroin self-administration via inhibition of the dopaminemediated reinforcing properties of heroin in the mesolimbic system. The anti-nicotine properties of baclofen are described in the paper by Fattore et al. (pp. 493–496), whose study shows the ability of baclofen to block dose-dependently the intravenous self-administration of nicotine in a unique paradigm using drug-naïve mice. Work from our laboratory by Colombo et al. (pp. 497–501) has demonstrated that baclofen induces a dose-dependent reduction of acquisition and maintenance of alcohol drinking behaviour in Sardinian alcohol-preferring (sP) rats, a rodent line selectively bred for high alcohol preference and consumption. These results have prompted an investigation in human alcoholics. The paper by Addolorato et al. (pp. 502–506) reports the results of the first double-blind, placebo-controlled survey of the effects of baclofen in promoting abstinence from alcohol and controlling alcohol craving. Despite the limited number of patients recruited and the relatively short duration of this study, the results of this preliminary investigation already suggest that baclofen possesses some efficacy in the treatment of alcoholism. Indeed, the daily administration of relatively low doses of baclofen resulted in a virtually complete suppression of the number of daily alcohol drinks and in a significant reduction in the compulsive and obsessive components of alcohol craving in baclofen-treated patients, when compared to placebo-dosed individuals. The results presented in the papers included in this journal issue clearly confirm the symposium title, i.e. that the pharmacological stimulation of GABAB receptors may constitute a novel strategy for the identification of medications in the addiction field. Accumulating lines of experimental evidence apparently support the fascinating hypothesis that the suppressant effects of GABAB receptor agonists on reinforcement produced by drugs of dependence may occur via a common mechanism, that is an inhibitory action on the stimulation produced by cocaine, heroin, nicotine and alcohol of the mesolimbic dopamine system. In agreement with this hypothesis, stimulation of the GABAB receptor might be beneficial also in those psychopathologies (e.g. schizophrenia) where inhibition of an aberrantly stimulated dopamine mesocorticolimbic neurotransmission may be advisable. Editor’s note: Of the five papers in this symposium, three received full peer review, namely those by Addolorato et al., Colombo et al. and Fattore et al. The other two papers (Brebner et al. and Xi and Stein) were not peer-reviewed, but received full editorial attention (A.A.-B.B.). 477 © 2002 Medical Council on Alcohol  (...truncated)