ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Selective breeding for high anxiety introduces a synonymous SNP that increases neuropeptide S receptor activity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Neuropeptide S modulation of learning and memory: a systematic review.Behavioral and brain functions : BBF · 2026Pooled it
- Sex-dependent role of Neuropeptide-S on anxiety, fear conditioning, and alcohol seeking in alcohol preferring rats.Neuropharmacology · 2025Article
- Beyond fur color: differences in socio-emotional behavior and the oxytocin system between male BL6 and CD1 mice in adolescence and adulthood.Frontiers in neuroscience · 2024Article
- A cluster of neuropeptide S neurons regulates breathing and arousal.Current biology : CB · 2023Article
- A Role for Neuropeptide S in Alcohol and Cocaine Seeking.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Effect of Neuropeptide S Administration on Ultrasonic Vocalizations and Behaviour in Rats with Low vs. High Exploratory Activity.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Pharmacology, Physiology and Genetics of the Neuropeptide S System.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Brain oxytocin: how puzzle stones from animal studies translate into psychiatry.Molecular psychiatry · 2021Review
- Turning strains into strengths for understanding psychiatric disorders.Molecular psychiatry · 2020Review
- Amygdala, neuropeptides, and chronic pain-related affective behaviors.Neuropharmacology · 2020Review
- Neuropeptide S receptor gene Asn107 polymorphism in obese male individuals in Pakistan.PloS one · 2020Article
- Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner.Translational psychiatry · 2019Article
- Neuropeptide S Ameliorates Cognitive Impairment of APP/PS1 Transgenic Mice by Promoting Synaptic Plasticity and Reducing Aβ Deposition.Frontiers in behavioral neuroscience · 2019Article
- Neuropeptide S Induces Acute Anxiolysis by Phospholipase C-Dependent Signaling within the Medial Amygdala.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Polymorphism in Tmem132d regulates expression and anxiety-related behavior through binding of RNA polymerase II complex.Translational psychiatry · 2018Article
- Neuropeptide S Counteracts Paradoxical Sleep Deprivation-Induced Anxiety-Like Behavior and Sleep Disturbances.Frontiers in cellular neuroscience · 2018Article
- Maternal Brain TNF-α Programs Innate Fear in the Offspring.Current biology : CB · 2017Article
- Neuropeptide S Activates Paraventricular Oxytocin Neurons to Induce Anxiolysis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Identification of the first biased NPS receptor agonist that retains anxiolytic and memory promoting effects with reduced levels of locomotor stimulation.Neuropharmacology · 2017Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 6 countries.
Funding
Abstract
Neuropeptide S (NPS) has generated substantial interest due to its anxiolytic and fear-attenuating effects in rodents, while a corresponding receptor polymorphism associated with increased NPS receptor (NPSR1) surface expression and efficacy has been implicated in an increased risk of panic disorder in humans. To gain insight into this paradox, we examined the NPS system in rats and mice bred for high anxiety-related behavior (HAB) versus low anxiety-related behavior, and, thereafter, determined the effect of central NPS administration on anxiety- and fear-related behavior. The HAB phenotype was accompanied by lower basal NPS receptor (Npsr1) expression, which we could confirm via in vitro dual luciferase promoter assays. Assessment of shorter Npsr1 promoter constructs containing a sequence mutation that introduces a glucocorticoid receptor transcription factor binding site, confirmed via oligonucleotide pull-down assays, revealed increased HAB promoter activity-an effect that was prevented by dexamethasone. Analogous to the human NPSR1 risk isoform, functional analysis of a synonymous single nucleotide polymorphism in the coding region of HAB rodents revealed that it caused a higher cAMP response to NPS stimulation. Assessment of the behavioral consequence of these differences revealed that intracerebroventricular NPS reversed the hyperanxiety of HAB rodents as well as the impaired cued-fear extinction in HAB rats and the enhanced fear expression in HAB mice, respectively. These results suggest that alterations in the NPS system, conserved across rodents and humans, contribute to innate anxiety and fear, and that HAB rodents are particularly suited to resolve the apparent discrepancy between the preclinical and clinical findings to date.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.