The antinociceptive activity of kappa- but not delta-opioid receptor agonists is maintained in morphine-tolerant neuropathic rats.
The antinociceptive effect of the preferential mu-opioid receptor agonist morphine (1 mg/kg i.v.), the delta-opioid receptor agonists, DTLET ([D-Thr2,Leu5]enkephalin-Thr) (3 and 6 mg/kg i.v.) and BUBUC ([D-Cys(StBu)2,Leu5]enkephalin-Thr(OtBu) (3 mg/kg i.v.), and the kappa-opioid receptor agonist U-69,593 (trans-3,4-dichloro-N-methyl-N-[7-(1-pyrrolidinyl)cyclohexil]benze neacetamide methanesulfonate) (0.25, 0.5 and 0.75 mg/kg i.v.) was evaluated in mononeuropathic (chronic constriction of the common sciatic nerve) rats. The rats were pretreated s.c. with 10 mg/kg of morphine, or saline, twice daily from day 12 to day 16 after the surgery. In morphine-pretreated rats, the antinociceptive effect of morphine on the vocalization threshold to paw pressure was greatly reduced, as compared to the saline-pretreated group. The antinociceptive effect of DTLET and BUBUC had also disappeared in the morphine-pretreated rats. By contrast, the potent antinociceptive effect of U-69,593 was not affected by the morphine pretreatment. Furthermore, the effect of U-69,593 was reversed by the specific kappa-opioid receptor antagonist nor-binaltorphimine (1 and 2 mg/kg i.v.). These results suggest that in mononeuropathic rats, morphine pretreatment results in cross-tolerance to delta- but not to kappa-opioid receptor agonists.
Catheline
G
G
Unité de Recherches de Physiopharmacologie du Systeme Nerveux, I.N.S.E.R.M., Paris, France.
Kayser
V
V
Idänpään-Heikkilä
J J
JJ
Guilbaud
G
G
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D044482:Benzeneacetamides; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D014828:Vocalization, Animal
D000701:Analgesics, Opioid; D044482:Benzeneacetamides; D009842:Oligopeptides; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; C067237:tyrosyl-cysteinyl(StBu)-glycyl-phenylalanyl-leucyl-threonyl(O-t-butyl); D009020:Morphine; C037653:deltakephalin; C045444:U 69593