Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 23, Pages -Publisher
MDPI
DOI: 10.3390/ijms222312956
Keywords
nociceptin; orphanin FQ; NOP receptor; stress; addiction
Funding
- National Institutes of Health [RO1 AA014351]
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Italian Ministry of University and Research PRIN [2017SXEXT5, FAR-2019]
- University of Camerino
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Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide that binds the NOP receptor and exerts anti-opioids effects; the NOP receptor is widely expressed in the brain, while N/OFQ is mainly localized in stress-related brain nuclei; preclinical evidence suggests that both NOP agonists and antagonists may be effective therapeutic approaches for substance use disorders.
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.
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