MODULATION OF MORPHINE-INDUCED ANTINOCICEPTION BY IBOGAINE AND NORIBOGAINE

The potential modulation of morphine antinociception by the putative a nti-addictive agent ibogaine and its active metabolite (noribogaine) w as investigated in rats with the radiant heat tail-flick test. Ibogain e pretreatment (40 mg/kg, i.p., 19 h) significantly decreased morphine (4 mg/kg, s.c.) antinociception, with no effects in the absence of mo rphine. However, co-administration of ibogaine (1-40 mg/kg, i.p.) and morphine (4 mg/kg, s.c.) exhibited a dose-dependent enhancement of mor phine antinociception. Co-administration of noribogaine (40 mg/kg, i.p .) and morphine also resulted in an increase in morphine antinocicepti on, while noribogaine pretreatment (19 h) had no effect on morphine an tinociception. The results show that ibogaine acutely potentiates morp hine antinociception and that noribogaine could be the active metaboli te responsible for this effect. However, the inhibitory effects of a 1 9 h ibogaine pretreatment, which resemble ibogaine-induced inhibition of morphine's stimulant properties, cannot be accounted for by noribog aine.