Baclofen antagonizes intravenous self-administration of nicotine in mice and rats.
OBJECTIVE
Gamma-aminobutyric acid (GABA)-ergic transmission plays an important role in modulating reinforcing effects of different drugs of misuse. In particular, stimulation of GABA(B) receptors negatively influences self-administration of cocaine, heroin, nicotine, alcohol and gamma-hydroxybutyric acid. The effect and specificity of the GABA(B) 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.
Fattore
Liana
L
CNR Centre for Neuropharmacology, Cittadella Universitaria di Monserrato, Cagliari, Italy.
Cossu
Gregorio
G
Martellotta
Maria Cristina
MC
Fratta
Walter
W
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D058786:GABA-B Receptor Agonists; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D018080:Receptors, GABA-B / Q000502:physiology; D012201:Reward; D012646:Self Administration; D013237:Stereoisomerism
D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D009538:Nicotine; D001418:Baclofen