Morphine‐6‐glucuronide‐Induced Locomotor Stimulation in Mice: Role of Opioid Receptors

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Abstract
Morphine‐6β‐glucuronide is a major metabolite of morphine with potent analgesic actions. To explore the importance of this opiate when administered 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 two opiates on a battery of 7 different locomotor activities were studied and compared to saline controls. A dose of 20 μmol/kg morphine‐6‐glucuronide resulted in more locomotion than the same dose of morphine, while at higher doses (up to 120 umol/kg), similar increases for most locomotor behaviours were recorded for both drugs. Pretreatment with naltrindole indicated that the S‐receptors play an equivalent but minor role in mediating both morphinc‐6‐glucuronide and morphine hyperlocomotion. Administration of high naltrexone doses (10 mg/kg) completely abolished the locomotor stimulation induced by both opiates. However, at intermediate naltrexone doses of 0.25 and 0.5 mg/kg, morphine‐induced behaviours was completely inhibited while morphine‐6‐glueuronide induced behaviours demonstrated partial resistance to naltrexone inhibition. The μ1‐specifie receptor antagonist naloxonazine caused 75% reduction of morphine induced behaviours and only 50% inhibition of morphine‐6‐glucuronide induced behaviors. Taken together our observations indicated general similarity but also marked differences between morphine and morphine‐6‐glucuronide with respect to opiate receptors mediating the locomotor stimulatory effect.