Dexamethasone blocking effects on mu- and delta-opioid-induced seizures involves kappa-opioid activity in the rabbit.
Previous data indicate that intracerebroventricular administration of agonists for mu- and delta-opioid receptors induces limbic seizures in rats, but no data are reported in rabbits. We found that the mu- and delta-opioid peptides [D-Ala(2)-N,Me-Phe(4)-Gly(5)-ol]enkephalin (DAMGO), beta-endorphin and deltorphin II, induced EEG non-convulsive hippocampal seizures, and changes in hippocampal background EEG, physical parameters and overt behaviour after central administration. Dexamethasone pre-treatment prevented DAMGO-, deltorphin II- and beta-endorphin-induced seizures as well as changes in background EEG, physical parameters and overt behaviour induced by mu-opioid agonists. Dexamethasone antagonism on opioid action was blocked by pre-treatment with a protein synthesis inhibitor, cycloheximide or by the kappa-opioid antagonist nor-binaltorphimine. Our data suggest that dexamethasone influences opioid actions at mu- and delta-receptors via a protein synthesis mechanism involving kappa-opioid receptors.
Di Giannuario
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Laboratorio di Farmacologia, Istituto Superiore di Sanità, Rome, Italy. dig@iss.it
Pieretti
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Sagratella
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Loizzo
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D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004569:Electroencephalography; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D011817:Rabbits; D017465:Receptors, Opioid, delta / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D001615:beta-Endorphin / Q000494:pharmacology
D000701:Analgesics, Opioid; D005938:Glucocorticoids; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060209:deltorphin II, Ala(2)-; D001615:beta-Endorphin; D003907:Dexamethasone