Secretin is a 27-amino acid brain-gut peptide from duodenal S-cells. We tested the effects of systemic administration of secretin to simulate its postprandial release on neuroendocrine neurons of the supraoptic nucleus (SON) in urethane-anesthetized female rats. Secretin dose-dependently increased the firing rate of oxytocin neurons, more potently than cholecystokinin, and dose-dependently increased plasma oxytocin concentration. The effect of secretin on SON vasopressin neurons was also predominantly excitatory, in contrast to the inhibitory actions of cholecystokinin. To explore the involvement of noradrenergic inputs in secretin-induced excitation, benoxathian, an alpha 1-adrenoceptor antagonist, was infused intracerebroventricularly. Benoxathian intracerebroventricular infusion blocked the excitation by secretin of both oxytocin and vasopressin neurons. To test the role of local noradrenaline release in the SON, benoxathian was microdialyzed onto the SON. The basal firing rate of oxytocin neurons was slightly reduced and the secretin-induced excitation was attenuated during benoxathian microdialysis. Hence, noradrenergic pathways mediate the excitation by systemic secretin of oxytocin neurons via alpha 1-adrenoceptors in the SON. As both systemic secretin and oxytocin are involved in regulating gastrointestinal functions and natriuresis, systemically released secretin might act partly through oxytocin.