Endogenous neuropeptide S tone influences sleep–wake rhythm in rats

Neuropeptide S (NPS) is an endogenous peptide that exerts wakefulness promoting, analgesic, and anx-iolytic effects when administered exogenously. However, it remains to be determined if endogenous NPStone is involved in the control of the diurnal sleep–wake cycle, or spontanous behavior.In this study, we examined the effects of the NPS receptor antagonist [D-Cys(tBu)5]NPS (2 and 20 nmol, icv) on physiological sleep and spontaneous locomotor behavior. The higher dose of [D-Cys(tBu)5]NPS decreased the amount of time spent in wakefulness [control 782.5 ± 25.5 min, treatment 751.7 ± 28.1 min; p < 0.05] and increased the time spent in NREMS [control 572.6 ± 17.2 min, treatment 600.2 ± 26.1 min; p < 0.05]. There was no statistically significant difference in time spent in REMS. Therewere no behavioral changes including abnormal gross motor behavior in response to [D-Cys(tBu)5]NPSadministration. Collectively these data suggest an involvement of the endogenous NPS/NPS receptorsystem in physiological sleep architecture.