GABAergic compounds-treating drug addiction: Preclinical

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During the period 01 Oct 04 to 30 Sept 05, moderate progress was made on this research project. We found that the GABA transaminase inhibitor gamma-vinyl-GABA (GVG, Vigabatrin) dose-dependently inhibits cocaine-triggered relapse to cocaine-seeking behavior in laboratory rats who has been pharmacologically detoxified and behaviorally extinguished from their prior cocaine-taking habits. In contrast to gamma-vinyl-GABA, systemic administration of gabapentin (another compound claimed in some previous studies to have anti-addiction properties for cocaine dependence) was found to have no effect whatever on cocaine-triggered relapse to cocaine-seeking or cocaine-taking behavior. By using in vivo brain microdialysis, we further found that gamma-vinyl-GABA dose-dependently inhibits the cocaine-induced increase in extracellular glutamate in the nucleus accumbens of the limbic forebrain, but does not affect the cocaine-induced increase in extracellular dopamine in the nucleus accumbens of the limbic forebrain. We further found that gabapentin has no effect on either extracellular dopamine or glutamate in the nucleus accumbens. When added to our previous extensive findings with gamma-vinyl-GABA, the present findings suggest that gamma-vinyl-GABA may have anti-addiction, anti-craving, and anti-relapse efficacy in human drug addiction.