Nitric oxide-mediated regulation of dopamine release in the hippocampus invivo

Infusion of N-methyl-D-aspartate (NMDA) into the hippocampus of freely movi ng rats produced a concentration-dependent decrease in the extracellular le vels of dopamine, an effect which was reversed by D-2-amino-5-phosphonovale ric acid (D-APS). To determine the involvement of nitric oxide (NO) in this response, two nitric oxide synthase (NOS) inhibitors, N-nitro-L-arginine m ethyl ester (L-NAME) and 7-nitroindazole (7-NI), were examined for their ab ility to modify both basal and NMDA-inhibited dopamine release. When infuse d alone both NOS inhibitors elicited an increase in extracellular dopamine concentration, moreover, when administered prior to the application of NMDA , the agonist failed to elicit a decrease in dopamine levels. Infusion of t he NO donor S-nitroso-N-acetylpenicillamine (SNAP) over a 30 min period cau sed either an increase or a decrease in dopamine release depending upon the concentration used. At the lower concentration (0.5 mM) SNAP promoted dopa mine release whilst at the higher concentration (5 mM), the donor elicited a long lasting reduction in basal dopamine levels. The effect of the lower concentration of SNAP was reversed by the prior application of D-APS, but t hat of the higher concentration was unaffected by the antagonist. (C) 2000 Elsevier Science Ltd. All rights reserved.