Immobilization induces acute nitric oxide production in the rat hypothalamus: A role of ionotropic glutamate receptors in the paraventricular nucleus

Production of nitric oxide (NO) in the hypothalamic paraventricular nucleus (PVN) was examined by microdialysis in rats subjected to immobilization (IMO) stress. A dialysis probe was implanted in the posterior magnocellular subdivision of the PVN and nitrite (NO2 ), an oxidized product of NO, was measured continuously. NO2 concentration in dialysate was enhanced to 156% after 30 min of IMO compared with the NO2 level before IMO. Intraperitoneal administration of N G -monomethyl-L-arginine (10 mg/kg), a NO synthase inhibitor, before IMO completely inhibited the increase of NO production that IMO was to induce. Depletion of catecholamines innervating the PVN by an injection of 6-hydroxydopamine into the lateral ventricle before the microdialysis had no suppressive effect on the increase of NO production by IMO. In contrast, NO2 levels in the PVN were lowered by continuous perfusion of the solution containing the ionotropic glutamate receptor antagonists 2-amino-5-phosphonovaleric acid (500 M) and 6-cyano7-nitroquinoxaline-2, 3 dione (50 M) through the dialysis probe, and the IMO-induced increase of NO production was attenuated by the treatment. These results suggest that catecholaminergic drive to the hypothalamus is not necessary for the IMO-induced increase of NO production and that ionotropic glutamate receptors play a role in the basal and IMOinduced NO production. (Endocrinology 145: 3603–3607, 2004)