Alcohol and Alcoholism Vol. 37, No. 5, pp. 495-498, 2002
© 2002 Medical Council on Alcohol
PROCEEDINGS OF A SYMPOSIUM ENTITLED: 'GABAB RECEPTORS: A TARGET OF NEW TREATMENTS FOR ALCOHOLISM AND DRUG ABUSE'
BACLOFEN ANTAGONIZES INTRAVENOUS SELF-ADMINISTRATION OF NICOTINE IN MICE AND RATS
Department of Neuroscience, University of Cagliari and
1 CNR Centre for Neuropharmacology, Cittadella Universitaria di Monserrato, SS 554, 09042 Monserrato, Cagliari, Italy
Received 1 March 2002; accepted 21 March 2002
ABSTRACT
— Aims: 
-Aminobutyric acid (GABA)-ergic transmission plays an important role in modulating reinforcing effects of different drugs of misuse. In particular, stimulation of GABAB receptors negatively influences self-administration of cocaine, heroin, nicotine, alcohol and -hydroxybutyric acid. The effect and specificity of the GABAB agonist baclofen on nicotine misuse were studied on two animal models of self-administration. Methods: The effects of RS baclofen and the two isomers R baclofen and S baclofen were studied on the acute nicotine self-administration in drug-naïve mice. The effect of RS baclofen was also studied in rats trained to chronically self-administer nicotine under a continuous reinforcement (FR1) schedule. Results: RS baclofen antagonizes nicotine intravenous self-administration at doses of 1.25–2.5 mg/kg intraperitoneally (i.p.). Furthermore, this effect is sterospecific. R baclofen completely prevented nicotine self-administration at the dose of 0.625 mg/kg i.p., whereas S baclofen was inactive up to the dose of 2.5 mg/kg i.p. In rats trained to self-administer nicotine, pretreatment with RS baclofen at the dose of 2.5 mg/kg i.p. significantly increased the rate of responding for nicotine. This effect was similar to the effect obtained when rats were pretreated with the nicotine central receptor antagonist mecamylamine (1 mg/kg i.p.). Conclusions: These data show that baclofen is able to antagonize nicotine-rewarding effects in mice and rats and suggest its potential clinical utility for the treatment of nicotine misuse.
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