Neuropeptides S is a stimulatory anxiolytic – a behavioral study in mice

Background and purpose. Neuropeptide S (NPS) was recently identified as the endogenous ligand of a previously orphan receptor now referred to as NPSR. In vivo, NPS produces a unique behavioral profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study we further evaluated the in vivo effects of supraspinal NPS in mice. Experimental approach. We assessed, in mice, the effects of intracerebroventricularly (i.c.v.) injected NPS on locomotor activity (LA), righting reflex (RR) recovery, and on anxiety states measured with the elevated plus maze (EPM) and stress induced hyperthermia (SIH) tests. Key results. NPS (0.01 – 1 nmol per mouse) caused a significant increase in LA in naive mice, in mice habituated to the test cages, and in animals sedated with diazepam 5 mg kg-1. In the RR assay, NPS dose dependently reduced the percent of animals losing the RR in response to diazepam 15 mg kg-1 and their sleeping time. In the EPM and SIH test, NPS dose dependently evokes anxiolytic-like effects by increasing the time (s) spent by animals in the open arms and reducing the stress-induced hyperthermic response, respectively. Conclusions and Implications. We provide further evidence that NPS acts as a novel modulator of arousal and anxiety-related behaviors by promoting a unique pattern of effects: stimulation associated with anxiolysis. Therefore NPSR ligands may represent innovative drugs for the treatment of sleep and anxiety disorders.