Central antinociception induced by mu-opioid receptor agonist morphine, but not delta- or kappa-, is mediated by cannabinoid CB1 receptor.
OBJECTIVE
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 mu-, delta- and kappa-opioid receptors.


METHODS
Nociceptive threshold to thermal stimulation was measured according to the tail-flick test in Swiss mice. Morphine (5 microg), SNC80 (4 microg), bremazocine (4 microg), AM251 (2 and 4 microg), AM630 (2 and 4 microg) and MAFP (0.1 and 0.4 microg) were administered by the intracerebroventricular route.


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 delta- and kappa-opioid receptor agonists were not affected by the cannabinoid antagonists. The antagonists alone caused no hyperalgesic or antinociceptive effects.


CONCLUSIONS
The results provide evidence for the involvement of cannabinoid CB(1) receptors in the central antinociception induced by activation of mu-opioid receptors by the agonist morphine. The release of endocannabinoids appears not to be involved in central antinociception induced by activation of kappa- and delta-opioid receptors.
Pacheco
Daniela da Fonseca
Dda F
Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, Belo Horizonte, Brazil.
Klein
André
A
Perez
Andréa Castro
AC
Pacheco
Cinthia Mara da Fonseca
CM
de Francischi
Janetti Nogueira
JN
Reis
Gláucia Maria Lopes
GM
Duarte
Igor Dimitri Gama
ID
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000378:metabolism / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000378:metabolism / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*
D000701:Analgesics, Opioid; D007211:Indoles; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C103505:AM 251; D009020:Morphine; C094023:iodopravadoline