EFFECTS OF PHARMACOLOGICAL INCREASES IN BRAIN GABA LEVELS ON COCAINE-INDUCED CHANGES IN EXTRACELLULAR DOPAMINE

Cocaine-induced increases in extracellular dopamine (DA) concentration s were measured using in vivo microdialysis techniques in the nucleus accumbens (NACC) of freely moving rats. In control animals, cocaine in creased extracellular DA concentrations approximately 482% 60 min foll owing administration, returning to baseline values 200 min later. When administered 2 h following an acute dose of gamma-vinyl-GABA (GVG, Vi gabatrin), cocaine-induced increases in extracellular DA were reduced to approximately 365% of baseline values. Chronic GVG administration f urther dose-dependently attenuated the effects of cocaine but did not alter the rate of increase or the rate of return to baseline values. T hese results indicate that GVG, a drug that increases brain GABA conce ntrations! is effective in attenuating the effect of cocaine on NACC D A. Taken with our earlier findings, these results support the targetin g of brain GABAergic systems as a potentially effective pharmacologic treatment strategy for cocaine addiction. (C) 1998 Wiley-Liss, Inc.(da gger)