MORPHINE-6-GLUCURONIDE - A POTENT STIMULATOR OF LOCOMOTOR-ACTIVITY INMICE

The present study tested the hypothesis that morphine glucuronides hav e stimulant properties by studying their effects on locomotor activity in mice. Drug-naive C57 BL/6J male mice were injected with saline, mo rphine, morphine-6-glucuronide (M6G) or morphine-3- glucuronide (M3G). In some experiments, mice were injected with saline or naloxone 5 min prior to drug treatment. Injection of 40 mg/kg morphine or M6G, but n ot M3G, significantly increased activity versus saline. The extent of activation induced by M6G was markedly higher than for morphine. Subse quent dose-response studies across a somewhat lower dose range using e quimolar doses of morphine and M6G (3-80 mu moles/kg) found that both drugs significantly increased locomotor activity beginning at 20 mu mo les/kg. M6G increased locomotor activity from 1.3 to 2.1 times more th an for equimolar doses of morphine. Pretreatment with naloxone (10 mg/ kg) completely abolished the locomotor stimulation induced by 32 mu mo les/kg morphine and M6G. These findings present evidence that M6G is a n active metabolite of morphine which has behaviorally stimulating eff ects and may play an important role in mediating the reinforcing prope rties of morphine in humans.