We recently identified neuromedin S (NMS) from the rat hypothalamus as an endogenous ligand for the FM-4/TGR-1 receptor distinct from neuromedin U. In the present study we examined the role of NMS in, the oxytocin release response to suckling stimulation by rat pups. Intracerebroventricular (icv) injection of NMS induced cFos expression in the paraventricular nucleus and supraoptic nucleus. Double immunohistochemical analysis revealed induction of cFos expression in a proportion of oxytocinergic neurons in both nuclei. In addition, icv injection of NMS stimulated oxytocin release close-dependently in intact rats, and increased milk secretion in lactating rats. On the other hand, icv injection of anti-NMS antiserum into lactating rats significantly suppressed suckling-induced milk ejection. These results Suggest that, in the rat, endogenous NMS plays an important role in the oxytocin release response to the suckling stimulus. (C) 2008 Published by Elsevier Inc.