Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance

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dc.authoridGunduz, Ozgur/0000-0002-2470-3021
dc.authoridUlugol, Ahmet/0000-0003-4643-1124
dc.authoridKaradag, Cetin Hakan/0000-0002-4763-986X
dc.authorwosidGÜNDÜZ, Özgür/AAH-8717-2019
dc.authorwosidGunduz, Ozgur/A-2351-2016
dc.authorwosidUlugol, Ahmet/V-9665-2019
dc.authorwosidKaradag, Cetin Hakan/H-4899-2013
dc.contributor.authorUlugol, Ahmet
dc.contributor.authorTopuz, Ruhan D.
dc.contributor.authorGunduz, Ozgur
dc.contributor.authorKizilay, Gulnur
dc.contributor.authorKaradag, Hakan C.
dc.date.accessioned2024-06-12T10:52:03Z
dc.date.available2024-06-12T10:52:03Z
dc.date.issued2016
dc.departmentTrakya Üniversitesien_US
dc.description.abstractIt 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.en_US
dc.description.sponsorshipTUBTAK [112S143]en_US
dc.description.sponsorshipThis work was supported by a grant from TUBTAK (112S143). We thank K. Duvan-Aydemir and Z.G. Todurga for technical assistance for analytical procedures and behavioral testing.en_US
dc.identifier.doi10.1111/fcp.12215
dc.identifier.endpage548en_US
dc.identifier.issn0767-3981
dc.identifier.issn1472-8206
dc.identifier.issue6en_US
dc.identifier.pmid27371029en_US
dc.identifier.scopus2-s2.0-84978518670en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage537en_US
dc.identifier.urihttps://doi.org/10.1111/fcp.12215
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18578
dc.identifier.volume30en_US
dc.identifier.wosWOS:000387597900006en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWiley-Blackwellen_US
dc.relation.ispartofFundamental & Clinical Pharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAntinociceptive Effecten_US
dc.subjectCannabinoiden_US
dc.subjectImmunohistochemistryen_US
dc.subjectNociceptinen_US
dc.subjectOrphanin FQen_US
dc.subjectToleranceen_US
dc.subjectWestern Blottingen_US
dc.subjectNitric-Oxide Productionen_US
dc.subjectNeuropathic Painen_US
dc.subjectMorphine-Toleranceen_US
dc.subjectOpioid Toleranceen_US
dc.subjectNerve Injuryen_US
dc.subjectCellular Mechanismsen_US
dc.subjectReceptor Agonistsen_US
dc.subjectPrecursor Proteinen_US
dc.subjectMiceen_US
dc.subjectDependenceen_US
dc.titleChanges in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive toleranceen_US
dc.typeArticleen_US

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