Prolonged antagonism of morphine-induced locomotor stimulation by kappa opioid agonists: enhancement by prior morphine exposure.
The selective kappa agonists U50488 (10 mg/kg, i.p.) and spiradoline (1 mg/kg, i.p.) attenuated the locomotor activating effects of a morphine challenge (5 mg/kg, i.p.) administered 19 h later in rats. This antagonism of morphine by a kappa agonist was reversed by the selective kappa antagonist, norbinaltorphimine (10 mg/kg, s.c.). Furthermore, the kappa opioid antagonism of morphine was enhanced by prior morphine exposure (2 doses of 30 mg/kg, i.p. administered once a day for 2 days). The present data suggest that kappa-micro opioid interactions may occur over time periods that exceed the acute durations of drug actions.
Pearl
S M
SM
Department of Pharmacology and Neuroscience, Albany Medical College, NY 12208, USA. spearl@ccgateway.amc.edu
Glick
S D
SD
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D009020:Morphine / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013997:Time Factors
D000700:Analgesics; D000701:Analgesics, Opioid; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C051272:spiradoline