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 morphi ne challenge (5 mg/kg, i.p.) administered 19 h later in rats. This ant agonism of morphine by a re agonist was reversed by the selective kapp a antagonist, norbinaltorphimine (10 mg/kg, s.c.). Furthermore, the ka ppa opioid antagonism of morphine was enhanced by prior morphine expos ure (2 doses of 30 mg/kg, i.p. administered once a day for 2 days). Th e present data suggest that kappa-mu opioid interactions may occur ove r time periods that exceed the acute durations of drug actions.