INHIBITION OF GLUTAMATE REUPTAKE POTENTIATES ENDOGENOUS NITRIC OXIDE-FACILITATED DOPAMINE EFFLUX IN THE RAT STRIATUM - AN IN-VIVO MICRODIALYSIS STUDY

The current study investigated the effects of the nitric oxide synthas e (NOS) substrate, N-G-hydroxy-L-arginine (H-ARG) and the selective gl utamate (GLU) reuptake inhibitor (2S)-trans-pyrrolidine-2,4-dicarboxyl ic acid (PDC) on striatal dopamine (DA) and glutamate (GLU) efflux in vivo. Concentric microdialysis probes were stereotaxically implanted i n the anterior-medial striatum of chloral hydrate-anesthetized rats. I ntra-striatal infusion of PDC (200 mu M) elevated extracellular (EC) D A and GLU levels concurrently over a 10 fraction collecting period wit hout affecting EC asparagine levels. Infusion of H-ARG (200 mu M) for six 20-min fractions, also significantly elevated EC DA levels. In the presence of PDC (200 mu M), co-perfusion of H-ARG (200 mu M) resulted in supra-additive increases in EC DA levels. The synergistic effect o f PDC and H-ARG infusion on DA efflux was attenuated by co-infusion of the NOS inhibitor, 7-nitroindazole (100-200 mu M). These results sugg est that while both endogenous NO and GLU regulate striatal DA efflux via facilitatory influences, enhanced glutamatergic tone on striatal N OS-containing neurons may potentiate NO-synthesis and subsequently NO- induced DA efflux. (C) 1997 Elsevier Science Ireland Ltd.