Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice.
OBJECTIVE
Neuropeptide S (NPS) was recently identified as the endogenous ligand of an orphan receptor, now referred to as the NPS receptor. In vivo, NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic-like effects. In the present study, we further evaluated the effects of in vivo supraspinal NPS in mice.


METHODS
Effects of NPS, injected intracerebroventricularly (i.c.v.), 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) were assessed in Swiss mice.


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 proportion 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 evoked anxiolytic-like effects by increasing the time spent by animals in the open arms and reducing the SIH response, respectively.


CONCLUSIONS
We provide further evidence that NPS acts as a novel modulator of arousal and anxiety-related behaviours by promoting a unique pattern of effects: stimulation associated with anxiolysis. Therefore, NPS receptor ligands may represent innovative drugs for the treatment of sleep and anxiety disorders.
Rizzi
A
A
Department of Experimental and Clinical Medicine, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy. a.rizzi@unife.it
Vergura
R
R
Marzola
G
G
Ruzza
C
C
Guerrini
R
R
Salvadori
S
S
Regoli
D
D
Calo
G
G
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000378:metabolism*; D001007:Anxiety / Q000378:metabolism* / Q000517:prevention & control / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D001833:Body Temperature Regulation; D002110:Caffeine / Q000008:administration & dosage; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000378:metabolism*; D003975:Diazepam / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity; D009479:Neuropeptides / Q000008:administration & dosage / Q000378:metabolism*; D012018:Reflex; D012890:Sleep / Q000187:drug effects; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
D014151:Anti-Anxiety Agents; D000697:Central Nervous System Stimulants; D009479:Neuropeptides; C506531:neuropeptide S, human; D002110:Caffeine; D003975:Diazepam