M. Grung et al., MORPHINE-6-GLUCURONIDE-INDUCED LOCOMOTOR STIMULATION IN MICE - ROLE OF OPIOID RECEPTORS, Pharmacology & toxicology, 82(1), 1998, pp. 3-10
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.