The End of My Addiction

receptor agonist baclofen reduced alcohol intake in selectively bred Sardinian alcohol-preferring (sP) rats tested under the home-cage, two-bottle choice regimen.
    Objectives
    The present study investigated the effect of baclofen on the appetitive, rather than consummatory, aspects of alcohol ingestion in sP rats.
    Methods
    Rats were trained to lever-press for oral alcohol (10%, v/v) or sucrose (3%, w/v) under a fixed-ratio schedule of 4. Once self-administration behavior was established, alcohol intake averaged approximately 0.7 g/kg over the 30-min session. Subsequently, the effect of the acute administration of baclofen (0, 1, 2 and 3 mg/kg, i.p.) on the extinction responding for alcohol and sucrose (defined as the maximal number of lever responses reached in the absence of reinforcement and used as index of motivation to consume alcohol and sucrose) was evaluated.
    Results
    All doses of baclofen produced a marked suppression of extinction responding for alcohol. Conversely, only the 3-mg/kg baclofen dose significantly affected extinction responding for sucrose. A separate open-field test indicated that baclofen (0, 1, 2 and 3 mg/kg, i.p.) did not affect spontaneous motor activity in sP rats.
    Conclusions
    These results suggest that baclofen may specifically reduce the motivational properties of alcohol; further, these results are in agreement with the recently reported anti-craving potential of baclofen in alcoholics.

 
    Abstract 4
    Fattore, L., Cossu, G., Martellotta, M. C. et al. (2002) Baclofen antagonizes intravenous self-administration of nicotine in mice and rats. Alcohol and Alcoholism 37, 495–498.
    Aims:-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.

 
    Abstract 5
    Brebner, K., Ahn, S., and Phillips, A. G. (2005) Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates. Psychopharmacology (Berlin) 177, 409–417.
    Rationale
    Recent reports have demonstrated that gamma-aminobutyric acid (GABA)-ergic compounds attenuate the reinforcing effects of cocaine in rats. Baclofen, a GABA B receptor agonist, appears to be particularly effective in this respect, suggesting that GABA B receptor activation is critically involved in mediating anti-cocaine effects. Amphetamine, like cocaine, is a psychomotor stimulant with high abuse potential in humans.
    Objectives
    The purpose of the present investigation was to determine whether baclofen may attenuate the reinforcing effects of d-amphetamine (dAMPH) in rats. Dose-response curves were generated to examine the effect of three doses of baclofen (1.8, 3.2 or 5.6 mg/kg, IP) on dAMPH intravenous self-administration (IVSA). Separate groups were trained to self-administer two doses of dAMPH (0.1 mg/kg or 0.2 mg/kg per injection) under either a fixed-ratio (FR) or progressive ratio (PR) schedule of reinforcement. Microdialysis was performed in an additional group of rats to examine the effect of baclofen on dAMPH-induced