Endogenous Orphanin FQ/Nociceptin Is Involved in the Development of Morphine Tolerance

  title={Endogenous Orphanin FQ/Nociceptin Is Involved in the Development of Morphine Tolerance},
  author={Shinjae Chung and S Pohl and Joanne Zeng and Olivier Civelli and Rainer K Reinscheid},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={262 - 267}
The neuropeptide orphanin FQ/nociceptin (OFQ/N) has been shown to counteract several effects of endogenous and exogenous opioids, and it has been proposed as an opioid-modulating agent involved in the development of morphine tolerance and dependence. However, conflicting results have been obtained from animal models using different protocols to induce morphine tolerance. Here, we report that both genetic and pharmacological blockade of OFQ/N signaling can effectively prevent development of… 

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The nociceptin/orphanin FQ receptor (NOP) as a target for drug abuse medications.
  • N. Zaveri
  • Biology, Psychology
    Current topics in medicinal chemistry
  • 2011
As with the case of buprenorphine, a mixed-action profile of NOP/opioid activity may provide a more effective drug to treat addiction to various abused substances and/or polydrug addiction.
The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence.
Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance
It is hypothesize that, similar to opioids, chronic cannabinoid + NOP antagonist administration may enhance N/OFQ levels and NOP receptor antagonism prevents development of tolerance to cannabinoid antinociception.
The Functional Antiopioid Action of the Ventrolateral Periaqueductal Gray Nociceptin/Orphanin FQ and Nociceptin Receptor System Underlies DAMGO Analgesic Tolerance
In DAMGO-tolerant rats, injection of the N/OFQ antagonist (±)-J 113397 (4 µg/1 µl), into the same site, restored the antinociceptive effect of DAMGO and confirmed that N/ OFQ acts as a functional opioid antagonist.
Involvement of the nociceptin opioid peptide receptor in morphine-induced antinociception, tolerance and physical dependence in female mice.
It is demonstrated that N/OFQ-NOP receptor system plays diverse roles in modulating pharmacological profiles of µ-opioid receptor agonists and that opioid analgesia has sex differences, and females experience greater pain and consume more opioids.


Functional studies using antibodies against orphanin FQ/nociceptin
Orphanin FQ is a functional anti-opioid peptide
Functional antagonism of μ-, δ- and κ-opioid antinociception by orphanin FQ
Functional antagonism of mu-, delta- and kappa-opioid antinociception by orphanin FQ.
It is concluded that OFQ functionally antagonizes mu (and) (opioid receptors, and may play a general role in opioid modulation, and was able to completely block supraspinal antinociception produced by all three receptor type-selective agonists.
Targeted disruption of the orphanin FQ/nociceptin gene increases stress susceptibility and impairs stress adaptation in mice.
OfQ/N appears to be crucially involved in the neurobiological regulation of stress-coping behavior and fear.
The effects of LY293558, an AMPA receptor antagonist, on acute and chronic morphine dependence
Enhanced Spinal Nociceptin Receptor Expression Develops Morphine Tolerance and Dependence
It is suggested that the spinal NOR system develops anti-opioid plasticity observed on morphine tolerance and dependence, as well as a parallel enhancement of NOR gene expression only in the spinal cord during chronic morphine treatments.
Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species
The findings of this study confirm the potent, ORL-1 receptor-mediated, anxiolytic-like effects of Ro64-6198, extending the findings across three species.
Morphine tolerance and dependence in the nociceptin receptor knockout mice
It is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.