Effects of pharmacologic increases in brain GABA levels on cocaine-induced changes in extracellular dopamine.
Cocaine-induced increases in extracellular dopamine (DA) concentrations were measured using in vivo microdialysis techniques in the nucleus accumbens (NACC) of freely moving rats. In control animals, cocaine increased extracellular DA concentrations approximately 482% 60 min following administration, returning to baseline values 200 min later. When administered 2 h following an acute dose of gamma-vinyl-GABA (GVG, Vigabatrin), cocaine-induced increases in extracellular DA were reduced to approximately 365% of baseline values. Chronic GVG administration further dose-dependently attenuated the effects of cocaine but did not alter the rate of increase or the rate of return to baseline values. These results indicate that GVG, a drug that increases brain GABA concentrations, is effective in attenuating the effect of cocaine on NACC DA. Taken with our earlier findings, these results support the targeting of brain GABAergic systems as a potentially effective pharmacologic treatment strategy for cocaine addiction.
Morgan
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Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Dewey
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D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; D003042:Cocaine; D004298:Dopamine