MORPHINE-6-GLUCURONIDE-INDUCED LOCOMOTOR STIMULATION IN MICE - ROLE OF OPIOID RECEPTORS

Morphine-6 beta-glucuronide is a major metabolite of morphine with pot ent analgesic actions. To explore the importance of this opiate when a dministered as a drug by its own or in morphine action, we studied the locomotor activity response to morphine and morphine-6-glucuronide in drug-naive C57 BL/6JBom mice. The effects of administration of the tw o opiates on a battery of 7 different locomotor activities were studie d and compared to saline controls. A dose of 20 mu mol/kg morphine-6-g lucuronide resulted in more locomotion than the same dose of morphine, while at higher doses (up to 120 mu mol/kg), similar increases for mo st locomotor behaviours were recorded for both drugs. Pretreatment wit h naltrindole indicated that the delta delta-receptors play an equival ent but minor role in mediating both morphine-6-glucuronide and morphi ne hyperlocomotion. Administration of high naltrexone doses (10 mg/kg) completely abolished the locomotor stimulation induced by both opiate s. However, at intermediate naltrexone doses of 0.25 and 0.5 mg/kg, mo rphine-induced behaviours was completely inhibited while morphine-6-gl ucuronide induced behaviours demonstrated partial resistance to naltre xone inhibition. The mu(1)-specific receptor antagonist naloxonazine c aused 75% reduction of morphine induced behaviours and only 50% inhibi tion of morphine-6-glucuronide induced behaviors. Taken together our o bservations indicated general similarity but also marked differences b etween morphine and morphine-6-glucuronide with respect to opiate rece ptors mediating the locomotor stimulatory effect.