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

Infusion of N-methyl-D-aspartate (NMDA) into the hippocampus of freely moving rats produced a concentration-dependent decrease in the extracellular levels of dopamine, an effect which was reversed by D-2-amino-5-phosphonovaleric acid (D-AP5). To determine the involvement of nitric oxide (NO) in this response, two nitric oxide synthase (NOS) inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), were examined for their ability to modify both basal and NMDA-inhibited dopamine release. When infused 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 the NO donor S-nitroso-N-acetylpenicillamine (SNAP) over a 30 min period caused either an increase or a decrease in dopamine release depending upon the concentration used. At the lower concentration (0.5 mM) SNAP promoted dopamine 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-AP5, but that of the higher concentration was unaffected by the antagonist.