Neuropeptide S Antagonizes Alarm Pheromones-induced Mouse Anxiety Via Its Receptor

Newly discovered neuropeptide S (NPS) is involved in many physiological regulations through its receptor (NPSR). NPSR mRNA is high expression in the assistant olfactory cortex and amygdale in mice suggesting that NPS-NPSR may be involved in modulation of pheromones in assistant olfactory system, though no evidences has been supplied so far. The present study was designed to investigate the effects of NPS-NPSR system on assistant olfactory system by alarm pheromones (APs), and the mechanism involved in.Method:Kunming male mice were used in this study, and randomly divided into 7 groups such as:(1) Vehicle+saline, (2) APs+saline, (3) APs+0.1 nmol NPS, (4) APs+0.5 nmol NPS, (5) APs+1 nmol NPS, (6) APs+0.5 nmol NPS+20 nmol [D-Val5]NPS, (7) APs+0.5 nmol NPS+40 nmol [D-Val5]NPS. A guide cannula was stereotaxically implanted above the right lateral ventricle under anesthesia, and then let them to recover for 7 days. APs were collected from donor mice by electrical stimulation of perianal. saline, NPS or NPSR antagonist were intracerebroventricularly injected through guide cannula 5 min before behavior test. Mice behaviors including the time outside hiding box, the conceal time, time of head out hiding box, grooming time, the time near stimuli and rearing time recorded within 10 min in the upgraded open field test with monitor of video.Results:Compared with the control, APs stimulated mice to significantly increase the conceal time (236.22±20.46 vs.335.55±1.94 s, P<0.01) and time of head out hiding box (16.43±1.52 vs.31.53±.82 s, P<0.01), and decrease the percentage of grooming time in the time outside box (7.18±.72% vs.1.70±.61%, P<0.01) and time outside box (323.76±21.15 vs.222.78±4.88 s, P<0.01).A range dose of 0.1,0.5 and 1 nmol of NPS administration, compared to control, increased the time outside box (331.36±7.50,332.45±3.91 and 332.02±52.25 s vs.222.78±4.88 s; P<0.05), and decreased the conceal time (235.92±3.22, 239.75 ±24.14 and 238.65±1.72 s vs.335.55±1.94 s; P<0.05), the time of head out hiding box (18.95±3.07,19.91±.34 and 21.16±.79 s vs.31.53±.82 s; P <0.01). Among these doses, the best efficiency was found by 0.5 nmol of NPS.40 nmol of [D-Val5]NPS significantly antagonized the effect of 0.5 nmol of NPS (P<0.05).Conclusion:APs causes anxiety in mice. NPS antagonizes APs-induced mouse anxiety via its receptor.