Nitric oxide modulates the release of serotonin in the rat hypothalamus

To investigate the effect of nitric oxide (NO) on the release of serotonin and its main metabolite, 5-hydroxyindoleacctic acid (5-HIAA), the posterior hypothalamus of the conscious rat was superfused through a push-pull cannula with drugs which either liberate NO, or inhibit NO synthase (NOS). The NO donors, linsidomine, diethylamine/nitric oxide (DEA/NO), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-glutathione (SNOG) and sodium nitroprusside influenced the release of serotonin in a biphasic way. Low concentrations of drugs diminished, while higher concentrations of these compounds enhanced the outflow of serotonin. The NOS inhibitors N-G-methyl-L-arginine methyl eater (L-NAME) and 7-nitroindazole (7-NINA) enhanced the serotonin release. A high concentration of L-NAME slightly diminished the outflow of serotonin. inhibition of the guanylyl cyclase by oxodiazolo[4,3]quinoxaline-one (ODQ) abolished the changes in serotonin outflow induced by both low and high concentrations of linsidomine. The extracellular concentration of the 5-HIAA was not influenced by the compounds used. These data suggest that endogenous NO modulates the release of serotonin in a biphasic and cGMP-dependent way. (C) 1999 Elsevier Science B.V. All rights reserved.