Conditioned place preference induced by morphine and morphine-6-glucuronide in mice

Abstract

Morphine-6-glucuronide (M6G), an active metabolite of morphine has been shown to produce analgesia and fewer side effects than morphine, and the introduction of M6G as a new drug for treatment of postoperative pain is planned in 2007. Following morphine intake in humans, the metabolites morphine-3-glucuronide (M3G) and M6G are present in substantial concentrations and for longer periods than the parent drug. The possible reward effects of the morphine glucuronides have previously not been well studied. In the present study, conditioned place preference (CPP) was recorded after conditioning with subcutaneous injections of 5, 10, 20, 30 or 50 μmol/kg morphine or M6G, or 240 or 500 μmol/kg M3G in C57BL/6J-Bom mice, using a biased two compartment (“closed” and “open”) counterbalanced paradigm. CPP was induced after treatment with both morphine and M6G with dose dependent increase up to 30 μmol/kg after treatment in the “closed” compartment. No dose response was observed in the “open” compartment, with maximal CPP after 10 μmol/kg morphine or M6G. M3G caused a tendency of condition place aversion (CPA), although not statistically significant. In the present study morphine and M6G demonstrated comparable reward effects, at doses that differed depending on which compartment the mice were conditioned in. M3G showed a tendency to exhibit aversive properties.