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Journal ArticleDOI

Neuropeptide S is a stimulatory anxiolytic agent: a behavioural study in mice

29 Jan 2009-British Journal of Pharmacology (Wiley-Blackwell)-Vol. 154, Iss: 2, pp 471-479
TL;DR: 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 2008
Citations
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Journal ArticleDOI
TL;DR: In this article, a multilevel approach was applied to further elucidate the role of neuropeptide S in the etiology of human anxiety, and the functional NPSR A/T (Asn 107 Ile) variant (rs324981) was investigated for association with panic disorder.
Abstract: Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn 107 Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case–control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli. Molecular Psychiatry (2011) 16, 938–948; doi:10.1038/mp.2010.81; published online 6 July 2010

159 citations

Journal ArticleDOI
TL;DR: The recently discovered Neuropeptide S and its cognate receptor represent a highly interesting system of neuromodulation with unique physiological effects that produces anxiolytic-like effects by acutely reducing fear responses as well as modulating long-term aspects of fear memory.

128 citations


Additional excerpts

  • ...(Xu et al., 2004; Vitale et al., 2008; Rizzi et al., 2008)....

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Journal ArticleDOI
TL;DR: Naval application of NPS seems to be a useful method in rodents for screening for behavioral or physiological effects before more specific and time-consuming, intracerebral methods are employed, and may represent a viable therapeutic approach for NPS treatment of patients with psychiatric illnesses such as anxiety or panic disorders.

117 citations


Cites background from "Neuropeptide S is a stimulatory anx..."

  • ...Thus, it reduced anxiety-related behavior in several relevant tests for non-social anxiety in both mice (Jüngling et al., 2008; Leonard et al., 2008; Rizzi et al., 2008; Xu et al., 2004) and rats (Slattery et al., 2008; Vitale et al., 2008; Wegener et al., 2011), mostly accompanied by an increase…...

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  • ...Thus, it reduced anxiety-related behavior in several relevant tests for non-social anxiety in both mice (Jüngling et al., 2008; Leonard et al., 2008; Rizzi et al., 2008; Xu et al., 2004) and rats (Slattery et al....

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Journal ArticleDOI
TL;DR: This is the most comprehensive identification of neuropeptide precursor proteins in an echinoderm to date, yielding new insights into the evolution of neuroPEptide signalling systems.
Abstract: Neuropeptides are evolutionarily ancient mediators of neuronal signalling in nervous systems. With recent advances in genomics/transcriptomics, an increasingly wide range of species has become accessible for molecular analysis. The deuterostomian invertebrates are of particular interest in this regard because they occupy an 'intermediate' position in animal phylogeny, bridging the gap between the well-studied model protostomian invertebrates (e.g. Drosophila melanogaster, Caenorhabditis elegans) and the vertebrates. Here we have identified 40 neuropeptide precursors in the starfish Asterias rubens, a deuterostomian invertebrate from the phylum Echinodermata. Importantly, these include kisspeptin-type and melanin-concentrating hormone-type precursors, which are the first to be discovered in a non-chordate species. Starfish tachykinin-type, somatostatin-type, pigment-dispersing factor-type and corticotropin-releasing hormone-type precursors are the first to be discovered in the echinoderm/ambulacrarian clade of the animal kingdom. Other precursors identified include vasopressin/oxytocin-type, gonadotropin-releasing hormone-type, thyrotropin-releasing hormone-type, calcitonin-type, cholecystokinin/gastrin-type, orexin-type, luqin-type, pedal peptide/orcokinin-type, glycoprotein hormone-type, bursicon-type, relaxin-type and insulin-like growth factor-type precursors. This is the most comprehensive identification of neuropeptide precursor proteins in an echinoderm to date, yielding new insights into the evolution of neuropeptide signalling systems. Furthermore, these data provide a basis for experimental analysis of neuropeptide function in the unique context of the decentralized, pentaradial echinoderm bauplan.

110 citations

Journal ArticleDOI
TL;DR: Evidence is provided for a facilitatory role of NPS in long-term memory, independent of memory content, possibly by acting as a salience signal or as an arousal-promoting factor.

109 citations


Cites background from "Neuropeptide S is a stimulatory anx..."

  • ...NPS and its cognate receptor, NPSR, modulate multiple brain functions, including sleep, arousal, and emotional processing (Xu et al, 2004; Okamura and Reinscheid, 2007; Rizzi et al, 2008; Leonard et al, 2008)....

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  • ...Pre-training and pre-retrieval administrations of NPS resulted in shorter IA latencies than vehicle treatment, most likely owing to the acute anxiolytic effects of NPS (Xu et al, 2004; Rizzi et al, 2008; Leonard et al, 2008; Jüngling et al, 2008)....

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References
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Journal ArticleDOI
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.

5,391 citations


"Neuropeptide S is a stimulatory anx..." refers methods in this paper

  • ...The EPM assay was carried out essentially as previously described by Pellow et al. (1985)....

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Journal ArticleDOI
TL;DR: The recommendations that follow have been updated from the proposals of a Technical Subcommittee set up by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification.
Abstract: The recommendations that follow have been updated from the proposals of a Technical Subcommittee set up by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (Jenkinson DH, Barnard EA, Hoyer D, Humphrey PPA, Leff P, and Shankley NP (1995) International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. IX. Recommendations on terms and symbols in quantitative pharmacology. Pharmacol Rev 47:255-266).

562 citations


"Neuropeptide S is a stimulatory anx..." refers methods in this paper

  • ...Data analysis The pharmacological terminology adopted in this paper is consistent with IUPHAR recommendations (Neubig et al., 2003)....

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  • ...The pharmacological terminology adopted in this paper is consistent with IUPHAR recommendations (Neubig et al., 2003)....

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Journal ArticleDOI
19 Aug 2004-Neuron
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.

474 citations


"Neuropeptide S is a stimulatory anx..." refers background or methods or result in this paper

  • ...…of different centrally mediated behaviours, including locomotor activity (LA) (Xu et al., 2004; Roth et al., 2006; Smith et al., 2006), wakefulness (Xu et al., 2004), anxiety (Xu et al., 2004; Leonard et al., 2007), food intake (Beck et al., 2005; Ciccocioppo et al., 2006; Smith et al., 2006;…...

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  • ...Similar results in terms of degree of stimulation, NPS potency, onset and duration of action were previously reported both in mice (Xu et al., 2004) and in rats (Smith et al., 2006)....

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  • ...NPS and its receptor are expressed in various tissues with the highest levels found in the brain, thyroid, salivary and mammary glands (Xu et al., 2004)....

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  • ...These findings parallel the results obtained by Xu et al. (2004) in rats in electroencephalographic studies, where NPS given i.c.v. in the same dose range (that is, 0.1 and 1 nmol) increases the amount of wakefulness and decreases SWS1, SWS2 and REM sleep....

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  • ...Following formal pairing with NPS, the GPR154 receptor was named the NPS receptor (Xu et al., 2004)....

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Journal ArticleDOI
09 Apr 2004-Science
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.
Abstract: Susceptibility to asthma depends on variation at an unknown number of genetic loci. To identify susceptibility genes on chromosome 7p, we adopted a hierarchical genotyping design, leading to the identification of a 133-kilobase risk-conferring segment containing two genes. One of these coded for an orphan G protein-coupled receptor named GPRA (G protein-coupled receptor for asthma susceptibility), which showed distinct distribution of protein isoforms between bronchial biopsies from healthy and asthmatic individuals. In three cohorts from Finland and Canada, single nucleotide polymorphism-tagged haplotypes associated with high serum immunoglobulin E or asthma. The murine ortholog of GPRA was up-regulated in a mouse model of ovalbumin-induced inflammation. Together, these data implicate GPRA in the pathogenesis of atopy and asthma.

456 citations


"Neuropeptide S is a stimulatory anx..." refers background in this paper

  • ...With respect to biological activity, genetic studies indicate a possible peripheral involvement of the NPS/NPS receptor system in chronic inflammatory conditions of barrier organs, such as asthma (Laitinen et al., 2004) and ulcerative colitis/ Crohn’s disease (D’Amato et al., 2007)....

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Journal ArticleDOI

390 citations


"Neuropeptide S is a stimulatory anx..." refers methods in this paper

  • ...…(2 ml per mouse) were given under light (just sufficient to produce a loss of the righting reflex) ether anaesthesia into the left ventricle according to the procedure described by Laursen and Belknap (1986) and routinely adopted in our laboratory (Rizzi et al., 2002; Gavioli et al., 2003)....

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