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), increased the locomotor activity of mice in a dose-dependent manner. Fifteen mg/kg of morphine and 20 mg/kg of morphine-6-glucuronide were almost equipotent. Subcutaneous administration of the universal opioid antagonist, 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 relatively higher doses of naloxone or naltrindole significantly reduced the hyperlocomotion induced by morphine-6-glucuronide (20 mg/kg). These findings suggest that agonistic actions at the opioid receptors, especially at the delta- and mu-receptors, contribute to the morphine-6-glucuronide-induced hyperlocomotion.