Enhancement of morphine antinociception by ibogaine and noribogaine in morphine-tolerant mice

The effects of ibogaine, an alkaloid isolated form the bark of the African shrub, Tabernathe iboga, and noribogaine, a metabolite of ibogaine, on morphine antinociception were determined in male Swiss-Webster mice. Mice were rendered tolerant to morphine by implanting them with a pellet containing 25 mg of morphine base for 3 days. Placebo pellet-implanted mice served as controls. The antinociception of morphine (10 mg/kg, s.c.) was determined alone or in combination with an appropriate dose of ibogaine or noribogaine. Tolerance to morphine developed as a result of morphine pellet implantation as evidenced by decreased antinociceptive response to morphine, Both ibogaine and noribogaine dose-dependently enhanced morphine antinociception in morphine-tolerant but not in morphine-naive mice. It is concluded that ibogaine and noribogaine enhance morphine antinociception in morphine-tolerant mice.