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Systemic cannabinoids produce CB₁-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT(7) and 5-HT(2A) receptors.
Eur J Pharmacol. 2010 Dec 15; 649(1-3):183-94.EJ

Abstract

Serotonin (5-HT) plays an important role in the descending control of pain. We evaluated the role of descending serotonergic pathways and spinal 5-HT₇ and 5-HT(2A) receptors in comparison to that of 5-HT(1A) and 5-HT₃ receptors in the antinociceptive effects of systemically administered cannabinoids. Antinociceptive effects were evaluated by radiant heat tail-flick and hot plate tests in Balb-C mice. The selective CB₁ receptor agonist, ACEA; a mixed CB₁ and CB₂ receptor agonist, WIN 55,212-2; and a selective CB₂ receptor agonist, GW405833, were given systemically to induce antinociception. Spinal 5-HT was depleted with intrathecal (i.th.) injection of 5,7-dihydroxytryptamine (5,7-DHT). Bilateral surgical lesions of the dorsolateral funiculus were performed. Selective 5-HT₇, 5-HT(2A), 5-HT(1A) and 5-HT₃ antagonists-SB-269970, ketanserin, WAY 100635 and ondansetron, respectively-were administered i.th. Risperidone, an atypical antipsychotic displaying 5-HT(2A) antagonism, also irreversibly binds to and inactivates the 5-HT₇ receptors. Thus, we also injected risperidone i.th. to elucidate the role of spinal 5-HT₇ and 5-HT(2A) receptors in cannabinoid-mediated antinociception. WIN 55,212-2 and ACEA produced dose-dependent antinociception, which were reversed by selective CB₁ receptor antagonist rimonabant. GW405833 did not produce any antinociception. The antinociceptive effects of WIN 55,212-2 and ACEA were totally absent in spinal 5-HT depleted and dorsolateral funiculus lesioned mice. I.th. administration of SB-269970, ketanserin, and risperidone, but not WAY 100635 or ondansetron, blocked both WIN 55,212-2- and ACEA-induced antinociception. These findings suggest that systemically administered cannabinoids interact with descending serotonergic pathways via CB₁-mediated mechanisms and exert a central antinociceptive effect involving spinal 5-HT₇ and 5-HT(2A) receptors.

Authors+Show Affiliations

Department of Medical Pharmacology, Gulhane Military Academy of Medicine, 06018 Ankara, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20868676

Citation

Seyrek, Melik, et al. "Systemic Cannabinoids Produce CB₁-mediated Antinociception By Activation of Descending Serotonergic Pathways That Act Upon Spinal 5-HT(7) and 5-HT(2A) Receptors." European Journal of Pharmacology, vol. 649, no. 1-3, 2010, pp. 183-94.
Seyrek M, Kahraman S, Deveci MS, et al. Systemic cannabinoids produce CB₁-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT(7) and 5-HT(2A) receptors. Eur J Pharmacol. 2010;649(1-3):183-94.
Seyrek, M., Kahraman, S., Deveci, M. S., Yesilyurt, O., & Dogrul, A. (2010). Systemic cannabinoids produce CB₁-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT(7) and 5-HT(2A) receptors. European Journal of Pharmacology, 649(1-3), 183-94. https://doi.org/10.1016/j.ejphar.2010.09.039
Seyrek M, et al. Systemic Cannabinoids Produce CB₁-mediated Antinociception By Activation of Descending Serotonergic Pathways That Act Upon Spinal 5-HT(7) and 5-HT(2A) Receptors. Eur J Pharmacol. 2010 Dec 15;649(1-3):183-94. PubMed PMID: 20868676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systemic cannabinoids produce CB₁-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT(7) and 5-HT(2A) receptors. AU - Seyrek,Melik, AU - Kahraman,Serdar, AU - Deveci,Mehmet Salih, AU - Yesilyurt,Ozgur, AU - Dogrul,Ahmet, Y1 - 2010/09/21/ PY - 2010/04/07/received PY - 2010/07/24/revised PY - 2010/09/14/accepted PY - 2010/9/28/entrez PY - 2010/9/28/pubmed PY - 2011/3/4/medline SP - 183 EP - 94 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 649 IS - 1-3 N2 - Serotonin (5-HT) plays an important role in the descending control of pain. We evaluated the role of descending serotonergic pathways and spinal 5-HT₇ and 5-HT(2A) receptors in comparison to that of 5-HT(1A) and 5-HT₃ receptors in the antinociceptive effects of systemically administered cannabinoids. Antinociceptive effects were evaluated by radiant heat tail-flick and hot plate tests in Balb-C mice. The selective CB₁ receptor agonist, ACEA; a mixed CB₁ and CB₂ receptor agonist, WIN 55,212-2; and a selective CB₂ receptor agonist, GW405833, were given systemically to induce antinociception. Spinal 5-HT was depleted with intrathecal (i.th.) injection of 5,7-dihydroxytryptamine (5,7-DHT). Bilateral surgical lesions of the dorsolateral funiculus were performed. Selective 5-HT₇, 5-HT(2A), 5-HT(1A) and 5-HT₃ antagonists-SB-269970, ketanserin, WAY 100635 and ondansetron, respectively-were administered i.th. Risperidone, an atypical antipsychotic displaying 5-HT(2A) antagonism, also irreversibly binds to and inactivates the 5-HT₇ receptors. Thus, we also injected risperidone i.th. to elucidate the role of spinal 5-HT₇ and 5-HT(2A) receptors in cannabinoid-mediated antinociception. WIN 55,212-2 and ACEA produced dose-dependent antinociception, which were reversed by selective CB₁ receptor antagonist rimonabant. GW405833 did not produce any antinociception. The antinociceptive effects of WIN 55,212-2 and ACEA were totally absent in spinal 5-HT depleted and dorsolateral funiculus lesioned mice. I.th. administration of SB-269970, ketanserin, and risperidone, but not WAY 100635 or ondansetron, blocked both WIN 55,212-2- and ACEA-induced antinociception. These findings suggest that systemically administered cannabinoids interact with descending serotonergic pathways via CB₁-mediated mechanisms and exert a central antinociceptive effect involving spinal 5-HT₇ and 5-HT(2A) receptors. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/20868676/Systemic_cannabinoids_produce_CB₁_mediated_antinociception_by_activation_of_descending_serotonergic_pathways_that_act_upon_spinal_5_HT_7__and_5_HT_2A__receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(10)00924-6 DB - PRIME DP - Unbound Medicine ER -