Effects of N-methyl-d-aspartate on extracellular citrulline level in the rat nucleus accumbens

In vivo microdialysis combined with high-performance liquid chromatography and electrochemical detection was used to study effects of intraaccumbal infusion of N-methyl-d-aspartate (NMDA) on the content of extracellular citrulline (a nitric oxide co-product) in the medial nucleus accumbens of Sprague-Dawley rats. The intraaccumbal NMDA infusion (10-1000 μM) dose-dependently increased the local dialysate citrulline levels (193 ± 7% and 258 ± 7% versus basal for the 100 and 1000 μM, respectively). The NMDA-induced increase of extracellular citrulline was completely prevented by intraaccumbal infusions through the dialysis probe both of 50 μM dizocilpine maleate (an NMDA antagonist) and of 0.5 mM N-nitro-l-arginine (a nitric oxide synthase inhibitor). Local infusion of N-nitro-l-arginine (0.5 mM) slightly decreased basal citrulline levels in the nucleus accumbens throughout the entire period of the infusion, whereas dizocilpine maleate (50 μM) had no long-lasting effect. These results suggest that NMDA receptor stimulation of the medial nucleus accumbens might cause a local nitric oxide synthase activation resulting in nitric oxide production in this brain area.