N-methyl-D-aspartate stimulates dopamine release through nitric oxide formation in the nucleus accumbens of rats.
Intracerebral microdialysis technique was utilized to study the effect of NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, on N-methyl-D-aspartate (NMDA)-induced dopamine overflow in the nucleus accumbens of unanesthetized, freely moving rats. Perfusion of 1 and 3 mM NMDA through the microdialysis probe dose-dependently increased the extracellular dopamine level in the nucleus accumbens. Coapplication of 0.5 mM D-(-)-2-amino-5-phosphonovaleric acid (D-AP5), a selective and competitive NMDA receptor antagonist, significantly reduced the dopamine overflow induced by 3 mM NMDA. Perfusion of 0.5 mM NG-nitro-L-arginine alone did not affect the basal dopamine level, whereas it suppressed the NMDA-evoked dopamine overflow in the nucleus accumbens when concurrently applied with 3 mM NMDA. These results suggest that NO mediates, at least in part, dopamine release resulting from NMDA receptor activation in the nucleus accumbens of rats.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Arai
I
I
Watanabe
S
S
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D016202:N-Methylaspartate; D001120:Arginine; D004298:Dopamine