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 synthase (NOS) substrate, N(G)-hydroxy-L-arginine (H-ARG) and the selective glutamate (GLU) reuptake inhibitor (2S)-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) on striatal dopamine (DA) and glutamate (GLU) efflux in vivo. Concentric microdialysis probes were stereotaxically implanted in the anterior-medial striatum of chloral hydrate-anesthetized rats. Intra-striatal infusion of PDC (200 microM) elevated extracellular (EC) DA and GLU levels concurrently over a 10 fraction collecting period without affecting EC asparagine levels. Infusion of H-ARG (200 microM) for six 20-min fractions, also significantly elevated EC DA levels. In the presence of PDC (200 microM), co-perfusion of H-ARG (200 microM) resulted in supra-additive increases in EC DA levels. The synergistic effect of PDC and H-ARG infusion on DA efflux was attenuated by co-infusion of the NOS inhibitor, 7-nitroindazole (100-200 microM). These results suggest that while both endogenous NO and GLU regulate striatal DA efflux via facilitatory influences, enhanced glutamatergic tone on striatal NOS-containing neurons may potentiate NO-synthesis and subsequently NO-induced DA efflux.
West
A R
AR
Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Galloway
M P
MP
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D017551:Microdialysis / Q000379:methods; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003998:Dicarboxylic Acids; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D009569:Nitric Oxide; D018698:Glutamic Acid; C068309:N(omega)-hydroxyarginine; D001120:Arginine; C083486:pyrrolidine-2,4-dicarboxylic acid; D004298:Dopamine