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Central antinociception induced by µ‐opioid receptor agonist morphine, but not δ‐ or κ‐, is mediated by cannabinoid CB 1 receptor
Author(s) -
da Fonseca Pacheco Daniela,
Klein André,
Perez Andréa Castro,
da Fonseca Pacheco Cinthia Mara,
de Francischi Janetti Nogueira,
Lopes Reis Gláucia Maria,
Duarte Igor Dimitri Gama
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00310.x
Subject(s) - agonist , cannabinoid , morphine , cannabinoid receptor , pharmacology , cannabinoid receptor agonists , opioid , opioid receptor , inverse agonist , chemistry , cannabinoid receptor type 2 , receptor , neuroscience , medicine , biology , biochemistry
Background and purpose: It has been demonstrated that cannabinoids evoke the release of endogenous opioids to produce antinociception; however, no information exists regarding the participation of cannabinoids in the antinociceptive mechanisms of opioids. The aim of the present study was to determine whether endocannabinoids are involved in central antinociception induced by activation of µ‐, δ‐ and κ‐opioid receptors. Experimental approach: Nociceptive threshold to thermal stimulation was measured according to the tail‐flick test in Swiss mice. Morphine (5 µg), SNC80 (4 µg), bremazocine (4 µg), AM251 (2 and 4 µg), AM630 (2 and 4 µg) and MAFP (0.1 and 0.4 µg) were administered by the intracerebroventricular route. Key results: The CB 1 ‐selective cannabinoid receptor antagonist AM251 completely reversed the central antinociception induced by morphine in a dose‐dependent manner. In contrast, the CB 2 ‐selective cannabinoid receptor antagonist AM630 did not antagonize this effect. Additionally, the administration of the anandamide amidase inhibitor, MAFP, significantly enhanced the antinociception induced by morphine. In contrast, the antinociceptive effects of δ‐ and κ‐opioid receptor agonists were not affected by the cannabinoid antagonists. The antagonists alone caused no hyperalgesic or antinociceptive effects. Conclusions and implications: The results provide evidence for the involvement of cannabinoid CB 1 receptors in the central antinociception induced by activation of µ‐opioid receptors by the agonist morphine. The release of endocannabinoids appears not to be involved in central antinociception induced by activation of κ‐ and δ‐opioid receptors.