DIFFERENTIAL-EFFECTS OF MORPHINE-6-GLUCURONIDE, AN ACTIVE METABOLITE OF MORPHINE, AND MORPHINE ON LOCOMOTOR-ACTIVITY IN MICE - INVOLVEMENT OF THE OPIOID RECEPTOR

Subcutaneous administration of morphine (2.5 to 20 mg/kg) or an active metabolite of morphine, morphine-6-glucuronide (2.5 to 20 mg/kg), inc reased the locomotor activity of mice in a dose-dependent manner. Fift een mg/kg of morphine and 20 mg/kg of morphine-6-glucuronide were almo st equipotent. Subcutaneous administration of the universal opioid ant agonist, naloxone, but not the delta-selective antagonist, naltrindole , significantly suppressed the hyperlocomotion induced by morphine (15 mg/kg). On the other hand the subcutaneous administration of relative ly higher doses of naloxone or naltrindole significantly reduced the h yperlocomotion induced by morphine-6-glucuronide (20 mg/kg). These fin dings suggest that agonistic actions at the opioid receptors, especial ly at the delta- and mu-receptors, contribute to the morphine-6-glucur onide-induced hyperlocomotion.