Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Nov 30;22(23):12956.
doi: 10.3390/ijms222312956.

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

Massimo Ubaldi  1 , Nazzareno Cannella  1 , Anna Maria Borruto  1 , Michele Petrella  1 , Maria Vittoria Micioni Di Bonaventura  1 , Laura Soverchia  1 , Serena Stopponi  1 , Friedbert Weiss  2 , Carlo Cifani  1 , Roberto Ciccocioppo  1
Affiliations
Review

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

Massimo Ubaldi et al. Int J Mol Sci. .

Abstract

Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

Keywords: NOP receptor; addiction; nociceptin/orphanin FQ; stress.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representantion of the relationship of the N/OFQ-NOP system with other neurocircuitries within the mesocorticolimbic reward system. Prefrontal Cortex (PFC); Nucleus Accumbens (NAc); Ventral Tegmental Area (VTA).
Figure 2
Figure 2
Schematic representantion of the relationship of the N/OFQ-NOP system with other neurocircuitries within the extrahypothalamic stress system. Prefrontal Cortex (PFC); Bed Nucleus of the Stria Terminalis (BNST); Central Nucleus of Amygdala (CeA); BasoLateral Nucleus of Amygdala (BLA); Locus Coeruleus (LC); Dorsal Raphe Nucleus (DRN).
Figure 3
Figure 3
Schematic representantion of the relationship of the N/OFQ-NOP system with other neurocircuitries within the HPA stress axis. Paraventricular Nucleus of the Hypothalamus (PVN).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Meunier J.C., Mollereau C., Toll L., Suaudeau C., Moisand C., Alvinerie P., Butour J.L., Guillemot J.C., Ferrara P., Monsarrat B., et al. Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature. 1995;377:532–535. doi: 10.1038/377532a0. - DOI - PubMed
    1. Reinscheid R.K., Nothacker H.P., Bourson A., Ardati A., Henningsen R.A., Bunzow J.R., Grandy D.K., Langen H., Monsma F.J., Jr., Civelli O. Orphanin FQ: A neuropeptide that activates an opioidlike G protein-coupled receptor. Science. 1995;270:792–794. doi: 10.1126/science.270.5237.792. - DOI - PubMed
    1. Mollereau C., Parmentier M., Mailleux P., Butour J.L., Moisand C., Chalon P., Caput D., Vassart G., Meunier J.C. ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett. 1994;341:33–38. doi: 10.1016/0014-5793(94)80235-1. - DOI - PubMed
    1. Civelli O. The orphanin FQ/nociceptin (OFQ/N) system. Results Probl. Cell Differ. 2008;46:1–25. - PubMed
    1. Mollereau C., Simons M.J., Soularue P., Liners F., Vassart G., Meunier J.C., Parmentier M. Structure, tissue distribution, and chromosomal localization of the prepronociceptin gene. Proc. Natl. Acad. Sci. USA. 1996;93:8666–8670. doi: 10.1073/pnas.93.16.8666. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources

-