During the period 01 Oct 05 to 30 Sept 06, significant 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 have been pharmacologically detoxified and behaviorally extinguished from their prior cocaine-taking habits. In contrast to gamma-vinyl-GABA, systemic administration of gabapentin (another putative GABAmimetic compound claimed in some previous reports from other research groups to have anti-cocaine-addiction properties) 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. We further found that gabapentin has no effect on either extracellular dopamine or glutamate in the nucleus accumbens. Additionally, we found that gamma-vinyl-GABA dose-dependently attenuates the increase in extracellular dopamine produced in the nucleus accumbens of the rodent limbic forebrain by methamphetamine. In addition, we found that gamma-vinyl-GABA dose-dependently attenuates methamphetamine-induced conditioned place preferences in laboratory rodents. We also found that subchronic (5-day) administration of gamma-vinyl-GABA significantly attenuates methamphetamine-triggered reactivation of methamphetamine-induced place preference. 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.
| O'Brien, Charles P; Gardner, Eliot L (2005) Critical assessment of how to study addiction and its treatment: human and non-human animal models. Pharmacol Ther 108:18-58 |
