Brain microdialysis plus high performance liquid chromatography and electrochemical detection were employed to study whether glutamate exerts direct presynaptic facilitation of dopamine (DA) release in the rat striatum. The perfusion of the dialysis probe with high-K+ Ringer solution (70 mM) increased DA and glutamate release 380.6 +/- 69.2% and 323.0 +/- 46.6% of preperfusion levels, respectively. Perfusion of 1 mM glutamate stimulated DA release by 250.7 +/- 30.6%, and coadministration of 2 mM glutamic acid diethylester (glutamate receptor blocking agent) significantly antagonized the glutamate response. The present results indicate presynaptic facilitation of the release of DA in the striatum by glutamate.