We investigated the possible involvement of neuromedin U (NMU) and neuromedin S (NMS) in thermoregulation in rats. Intracerebroventricular (icy) injection of NMU or NMS increased the back surface temperature (BST) in a dose-dependent manner during both the light and dark periods. Pre-treatment with the beta 3 blocker SR59230A, and the cyclooxygenase blocker indomethacin, inhibited the increase in BS-T induced by NMS. Icy injection of NMS and NMU increased the expression of mRNAs for prostaglandin E synthase and cyclooxygenase 2 (COX2) in the hypothalamus, and that of mRNA for uncoupling protein 1 (UCP1) in the brown adipose tissue. Comparison of thermogenesis in terms of body temperature under normal and cold conditions revealed that NMS-KO and double-KO mice had a significantly low BS-T during the active phase, whereas NMU-KO mice did not. Exposure to low temperature decreased the BS temperature in all KO mice, but BST was lower in NMS-KO and double-KO mouse than in NMU-KO mice. Calorie and oxygen consumption was also significantly lower in all KO mice than in wild-type mice during the dark period. These results suggest that NMU and NMS are involved in thermoregulation via the prostaglandin E2 and beta 3 adrenergic receptors, but that endogenous NMS might play a more predominant role than NMU. (C) 2016 Elsevier Inc. All rights reserved.