Geraniin attenuates naloxone-precipitated morphine withdrawal and morphine-induced tolerance in mice

BACKGROUND AND AIM Potentially life-threatening and unpleasant side effects associated with some analgesics have fueled the drive for the search for more analgesics with better side effect profiles. Geraniin, the most dominant secondary metabolite in the aqueous extract of the aerial parts of Phyllanthus muellerianus, has been shown to possess antinociceptive properties mediated partly by opioidergic mechanisms. The purpose of this study is to determine whether geraniin exhibits tolerance and if it is able to ameliorate withdrawal signs in naloxone-precipitated morphine withdrawal. MATERIALS AND METHODS After chronic treatment of mice with geraniin orally, the formalin test was used to ascertain whether tolerance will develop to its antinociceptive effects and if there is morphine-induced tolerance cross-generalization with geraniin. The effect of geraniin on naloxone-precipitated morphine withdrawal signs in morphine-dependent mice was also investigated. RESULTS Geraniin (3-30 mg/kg) did not produce any tolerant effects after chronic administration and there was also no cross-generalization with the tolerant effects of morphine. Geraniin did not induce withdrawal signs but significantly reduced the number of jumps in morphine-dependent mice. CONCLUSION Geraniin does not produce any tolerant effects like morphine and also reduced the signs associated with naloxone-precipitated morphine withdrawal in mice.