Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice
Anna Rizzi,Raffaella Vergura,Giuliano Marzola,Chiara Ruzza,Remo Guerrini,Severo Salvadori,Domenico Regoli,Girolamo Calo +7 more
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TLDR
The effects of in vivo supraspinal NPS in mice are evaluated and it is shown that in vivo NPS produces a unique behavioural profile by increasing wakefulness and exerting anxiolytic‐like effects.Abstract:
Background and purpose:
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.
Experimental approach:
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.
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 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 and implications:
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.
British Journal of Pharmacology (2008) 154, 471–479; doi:10.1038/bjp.2008.96; published online 31 March 2008read more
Citations
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[tBu-D-Gly5]NPS, a pure and potent antagonist of the neuropeptide S receptor: in vitro and in vivo studies.
Chiara Ruzza,Anna Rizzi,Valeria Camarda,Alice Pulga,Giuliano Marzola,Monica Filaferro,Chiara Novi,Valentina Ruggieri,Erika Marzola,Giovanni Vitale,S. Salvadori,Remo Guerrini,Girolamo Calo +12 more
TL;DR: It is demonstrated that [(t)Bu-D-Gly(5)]NPS behaves both in vitro and in vivo as a pure and potent NPSR antagonist and represents a novel and useful tool for investigating the pharmacology and neurobiology of the NPS/NPSR system.
Journal ArticleDOI
Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats.
TL;DR: A small-molecule NPSR antagonist (RTI-118) was developed and tested and supported the hypothesis that antagonism of the neuropeptide S receptor may ultimately show efficacy in reducing cocaine use and relapse.
Journal ArticleDOI
Human Neuropeptide S Receptor Is Activated via a Gαq Protein-biased Signaling Cascade by a Human Neuropeptide S Analog Lacking the C-terminal 10 Residues
Yuan Liao,Bin Lu,Qiang Ma,Gang Wu,Xiangru Lai,Jiashu Zang,Ying Shi,Dongxiang Liu,Feng Han,Naiming Zhou +9 more
TL;DR: Results demonstrate that hNPS-(1–10) is a biased agonist favoring Gαq-dependent signaling, and may represent a valuable chemical probe for further investigation of the therapeutic potential of human NPS receptor-directed signaling in vivo.
Journal ArticleDOI
Anti-stress neuropharmacological mechanisms and targets for addiction treatment: A translational framework.
TL;DR: This selective review focuses on emerging pharmacotherapies with potential for reducing stress-potentiated seeking and consumption of nicotine, alcohol, marijuana, cocaine, and opioids (i.e., key phenotypes for the most commonly abused substances).
Journal ArticleDOI
Central prostaglandin D2 exhibits anxiolytic-like activity via the DP1 receptor in mice
TL;DR: This paper found that prostaglandin (PG) D 2, the most abundant PG produced in the central nervous system (CNS), exhibited anxiolytic-like activity at a dose of 10-100 pmol/mouse after intracerebroventricular (i.c.v.) administration in the elevated plus-maze test in mice.
References
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TL;DR: A novel test for the selective identification of anxiolytic and anxiogenic drug effects in the rat is described, using an elevated + -maze consisting of two open arms and two enclosed arms, which showed that behaviour on the maze was not clearly correlated either with exploratory head-dipping or spontaneous locomotor activity.
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Neuropeptide S: A Neuropeptide Promoting Arousal and Anxiolytic-like Effects
Yan Ling Xu,Rainer K. Reinscheid,Salvador Huitron-Resendiz,Stewart D. Clark,Zhiwei Wang,Steven H.S. Lin,Fernando A. Brucher,Joanne Zeng,Nga Kim Ly,Steven J. Henriksen,Luis de Lecea,Olivier Civelli +11 more
TL;DR: It is reported that a neuropeptide, NPS, potently modulates wakefulness and could also regulate anxiety, and it is shown that the LC region encompasses distinct nuclei expressing different arousal-promoting neurotransmitters.
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Characterization of a common susceptibility locus for asthma-related traits
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TL;DR: In three cohorts from Finland and Canada, single nucleotide polymorphism–tagged haplotypes associated with high serum immunoglobulin E or asthma or asthma implicate GPRA in the pathogenesis of atopy and asthma.