ArticleProceedings of the National Academy of Sciences of the United States of America2023
Activation of the nociceptin/orphanin-FQ receptor promotes NREM sleep and EEG slow wave activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Efficacy of electroacupuncture in the treatment of insomnia in cancer patients: A meta-analysis.Medicine · 2025Pooled it
- Structural factors for receptor binding and activation of the Nociceptin opioid receptor by full and partial agonists.Biochemical pharmacology · 2026Article
- Design of New Potent, Selective, and Long-Acting NOP Receptor Agonists through Multiple Sequential d-Amino Acid Substitutions of [Arg14 Lys15]N/OFQ(1-15)-NH2.Journal of medicinal chemistry · 2026Article
- The Therapeutic Potential of Dual NMR (NOP/MOP) Agonism in Pain Management.Pain and therapy · 2026Review
- Mu-opioid and nociceptin receptors show divergent, cell-type-specific actions in the mesocorticolimbic reward system in opioid use disorder.Frontiers in cellular neuroscience · 2026Review
- Synthesis and Pharmacological Characterization of Nociceptin/Orphanin FQ Dimeric Ligands.Journal of medicinal chemistry · 2025Article
- Causal effects of sleep behaviors on temporomandibular disorders and pain: a bidirectional mendelian randomization study.Journal of oral & facial pain and headache · 2025Article
- NOP agonist AT-403 promoted sleep in lactic acid-induced acute pain model.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Prospects of Electrocorticography in Neuropharmacological Studies in Small Laboratory Animals.Brain sciences · 2024Review
- Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.Nature communications · 2024Article
- Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release.bioRxiv : the preprint server for biology · 2024Article
- Targeting Nociceptin/Orphanin FQ receptor to rescue cognitive symptoms in a mouse neuroendocrine model of chronic stress.Molecular psychiatry · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Sleep/wake control involves several neurotransmitter and neuromodulatory systems yet the coordination of the behavioral and physiological processes underlying sleep is incompletely understood. Previous studies have suggested that activation of the Nociceptin/orphanin FQ (N/OFQ) receptor (NOPR) reduces locomotor activity and produces a sedation-like effect in rodents. In the present study, we systematically evaluated the efficacy of two NOPR agonists, Ro64-6198 and SR16835, on sleep/wake in rats, mice, and Cynomolgus macaques. We found a profound, dose-related increase in non-Rapid Eye Movement (NREM) sleep and electroencephalogram (EEG) slow wave activity (SWA) and suppression of Rapid Eye Movement sleep (REM) sleep in all three species. At the highest dose tested in rats, the increase in NREM sleep and EEG SWA was accompanied by a prolonged inhibition of REM sleep, hypothermia, and reduced locomotor activity. However, even at the highest dose tested, rats were immediately arousable upon sensory stimulation, suggesting sleep rather than an anesthetic state. NOPR agonism also resulted in increased expression of c-Fos in the anterodorsal preoptic and parastrial nuclei, two GABAergic nuclei that are highly interconnected with brain regions involved in physiological regulation. These results suggest that the N/OFQ-NOPR system may have a previously unrecognized role in sleep/wake control and potential promise as a therapeutic target for the treatment of insomnia.
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