EVIDENCE FOR ROLES OF KAPPA-OPIOID AND NMDA RECEPTORS IN THE MECHANISM OF ACTION OF IBOGAINE

Ibogaine, a putatively anti-addictive alkaloid, binds to kappa-opioid and NMDA receptors. In the present study we investigated the roles of kappa-opioid and NMDA actions in mediating ibogaine's (40 mg/kg, i.p.) behavioral and neurochemical effects in rats. A combination of a kapp a-opioid antagonist (norbinaltorphimine, 10 mg/kg, s.c.) and a NMDA ag onist (NMDA, 20 mg/kg, i.p.) partially prevented ibogaine-induced inhi bition of intravenous morphine self-administration and ibogaine-induce d antagonism of morphine-induced locomotor stimulation. The combinatio n, as well as norbinaltorphimine and NMDA alone, blocked the acute eff ects of ibogaine on dopamine release and metabolism in the striatum. T he data suggest that both kappa-opioid agonist and NMDA antagonist act ions of ibogaine contribute to its putative anti-addictive effects.