Central Neuropeptide S inhibits food intake in mice through activation of Neuropeptide S receptor

Neuropeptide S (NPS), the endogenous ligand of NPS receptor (NPSR), can regulate a variety of biological functions, including arousal, anxiety, locomotion, memory and drug abuse. Previous studies have shown that central NPS inhibited food intake in rats and chicks. In the present study, we investigated the role of central NPS on food intake in fasted mice, and detected the underlying mechanism(s) by using NPSR antagonist [D-Val(5)]NPS and Corticotropin-Releasing Factor 1 (CRF₁) Receptor antagonist NBI-27914. The present results indicated that intracerebroventricular injection of NPS (0.001-0.1 nmol) dose-dependently inhibited food intake in fasted mice. The anorectic effect of NPS reached the maximum at the dose of 0.1 nmol, which could be antagonized by co-injection of 10 nmol NPSR antagonist [D-Val(5)]NPS. Furthermore, CRF₁ receptor antagonist NBI-27914 at the dose of 2 μg antagonized the hyperlocomotor action of NPS, but did not affect the role of NPS on food intake. In conclusion, our results demonstrated central NPS inhibited food intake in fasted mice, mediated by its cognate NPSR, but not by CRF₁ receptor.