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Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance
Author(s) -
Ulugol Ahmet,
Topuz Ruhan D.,
Gunduz Ozgur,
Kizilay Gulnur,
Karadag Hakan C.
Publication year - 2016
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12215
Subject(s) - nociceptin receptor , nop , periaqueductal gray , locus coeruleus , nociception , dorsal raphe nucleus , cannabinoid , pharmacology , endocrinology , medicine , opioid , antagonist , chemistry , receptor , opioid peptide , serotonin , midbrain , central nervous system , serotonergic
It has been indicated that acute and chronic morphine administrations enhance nociceptin/orphanin FQ (N/ OFQ ) levels in the brain, which might play role in the development of tolerance to the antinociceptive effect of morphine. Accordingly, N/ OFQ receptor ( NOP ) antagonists have been shown to prevent the development of antinociceptive tolerance to morphine. Our aim is to observe whether cannabinoids, similarly to opioids, enhance N/ OFQ levels in pain‐related brain regions and whether antagonism of NOP receptors attenuates the development of tolerance to the antinociceptive effect of cannabinoids. Hot plate and Tail flick tests are used to assess the antinociceptive response in Sprague‐Dawley rats. N/ OFQ levels are measured in cortex, amygdala, hypothalamus, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains using Western blotting and immunohistochemistry. Within 9 days, animals became completely tolerant to the antinociceptive effect of the cannabinoid agonist WIN 55,212‐2 (2, 4, 6 mg/kg, i.p.). Chronic administration of JTC ‐801, a NOP receptor antagonist, at a dose that exerted no effect on its own (1 mg/kg, i.p.), attenuated development of tolerance to the antinociceptive effect of WIN 55,212‐2 (4 mg/kg, i.p.). Western blotting and immunohistochemistry results showed that N/ OFQ levels significantly increased in amygdala, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains when WIN 55,212‐2 was combined with JTC ‐801. We 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.