The regulation of NMDA-evoked dopamine release by nitric oxide in the frontal cortex and raphe nuclei of the freely moving rat

Abstract

The role of nitric oxide (NO) in the N-methyl- d-aspartate (NMDA)-regulated release of dopamine (DA) in the frontal cortex and raphe nuclei of the freely moving rat was measured using in vivo microdialysis. The effects of infusing the NMDA antagonist 2-amino-5-phosphonopentanoic acid (AP5; 100 μM), neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7NI; 1 mM) or the nitric oxide donor S-nitroso- N-acetylpenicillamine (SNAP; 500 μM–5 mM) were studied. The infusion of NMDA caused a significant decrease in DA levels in both regions and these effects were reversed by AP5. AP5 alone was seen to increase DA, indicating that NMDA receptors tonically regulate DA release in these brain regions. 7NI also increased extracellular DA levels when administered alone and reversed the effects of NMDA in both regions. The NO donor SNAP (500 μM–1 mM) caused a dose-dependent decrease in extracellular DA in the RN. However in the frontal cortex the highest concentration of SNAP caused extracellular dopamine to increase. These results suggest that the regulation of NMDA-evoked DA release by NO occurs in both of the brain regions studied, although the manner in which the regulation occurs seems to differ between the two.