Dexamethasone-induced selective inhibition of the central mu opioid receptor: functional in vivo and in vitro evidence in rodents.
1. Endogenous corticosteroids and opioids are involved in many functions of the organism, including analgesia, cerebral excitability, stress and others. Therefore, we considered it important to gain information on the functional interaction between corticosteroids and specific opioid receptor subpopulations. 2. We have found that systemic administration (i.p.) of the potent synthetic corticosteroid, dexamethasone, reduced the antinociception induced by the highly selective mu agonist, DAMGO or by less selective mu agonists morphine and beta-endorphin administered i.c.v.. On the contrary dexamethasone exerted little or no influence on the antinociception induced by a delta 1 agonist, DPDPE and a delta 2 agonist deltorphin II. Dexamethasone potentiated the antinociception induced by the kappa agonist, U50,488. 3. In experiments performed in an in vitro model of cerebral excitability in the rat hippocampal slice, dexamethasone strongly prevented both the increase of the duration of the field potential recorded in CA1, and the appearance and number of additional population spikes induced by mu receptor agonists. 4. In both models pretreatment with cycloheximide, a protein synthesis inhibitor, prevented the antagonism by dexamethasone of responses to the mu opioid agonists. 5. Our data indicate that in the rodent brain there is an important functional interaction between the corticosteroid and the opioid systems at least at the mu receptor level, while delta and kappa receptors are modulated in different ways.
Pieretti
S
S
Istituto Superiore di Sanita, Roma, Italy.
Di Giannuario
A
A
Domenici
M R
MR
Sagratella
S
S
Capasso
A
A
Sorrentino
L
L
Loizzo
A
A
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D001615:beta-Endorphin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000700:Analgesics; D004745:Enkephalins; D009842:Oligopeptides; D011759:Pyrrolidines; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060209:deltorphin II, Ala(2)-; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D003907:Dexamethasone; D020881:Enkephalin, D-Penicillamine (2,5)-