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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.
Fundam Clin Pharmacol. 2016 Dec; 30(6):537-548.FC

Abstract

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.

Authors+Show Affiliations

Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey.Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey.Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey.Department of Histology and Embryology, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey.Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030, Edirne, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27371029

Citation

Ulugol, Ahmet, et al. "Changes in Nociceptin/orphanin FQ Levels in Rat Brain Regions After Acute and Chronic Cannabinoid Treatment in Conjunction With the Development of Antinociceptive Tolerance." Fundamental & Clinical Pharmacology, vol. 30, no. 6, 2016, pp. 537-548.
Ulugol A, Topuz RD, Gunduz O, et al. Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance. Fundam Clin Pharmacol. 2016;30(6):537-548.
Ulugol, A., Topuz, R. D., Gunduz, O., Kizilay, G., & Karadag, H. C. (2016). Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance. Fundamental & Clinical Pharmacology, 30(6), 537-548. https://doi.org/10.1111/fcp.12215
Ulugol A, et al. Changes in Nociceptin/orphanin FQ Levels in Rat Brain Regions After Acute and Chronic Cannabinoid Treatment in Conjunction With the Development of Antinociceptive Tolerance. Fundam Clin Pharmacol. 2016;30(6):537-548. PubMed PMID: 27371029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance. AU - Ulugol,Ahmet, AU - Topuz,Ruhan D, AU - Gunduz,Ozgur, AU - Kizilay,Gulnur, AU - Karadag,Hakan C, Y1 - 2016/07/14/ PY - 2015/11/25/received PY - 2016/06/06/revised PY - 2016/06/29/accepted PY - 2016/7/3/pubmed PY - 2017/3/30/medline PY - 2016/7/3/entrez KW - Western blotting KW - antinociceptive effect KW - cannabinoid KW - immunohistochemistry KW - nociceptin/orphanin FQ KW - tolerance SP - 537 EP - 548 JF - Fundamental & clinical pharmacology JO - Fundam Clin Pharmacol VL - 30 IS - 6 N2 - 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. SN - 1472-8206 UR - https://www.unboundmedicine.com/medline/citation/27371029/Changes_in_nociceptin/orphanin_FQ_levels_in_rat_brain_regions_after_acute_and_chronic_cannabinoid_treatment_in_conjunction_with_the_development_of_antinociceptive_tolerance_ L2 - https://doi.org/10.1111/fcp.12215 DB - PRIME DP - Unbound Medicine ER -