Noribogaine generalization to the ibogaine stimulus: Correlation with noribogaine concentration in rat brain

The discriminative stimulus effects of ibogaine and noribogaine in rats hav e been examined in relation to their concentrations in blood plasma and bra in regions and to receptor systems through which they have been proposed to act. Ants were trained to discriminate ibogaine (10 mg/kg IP), the NMDA an tagonist dizocilpine (0.08 mg/kg IP) or the kappa-opioid agonist U50,488 (5 mg/kg IP) from vehicle in a standard two-lever operant conditioning proced ure with a tandem VI-FR schedule of food reinforcement. Only rats trained o n ibogaine generalized to noribogaine, which was approximately twice as pot ent as the parent compound. Noribogaine was detected in plasma and brain af ter administration of ibogaine and noribogaine. At the ED50 doses for the d iscriminative effect, the estimated concentrations of noribogaine in plasma , cerebral cortex, and striatum were similar regardless of whether ibogaine or noribogaine was administered. The findings suggest that the metabolite noribogaine may be devoid of NMDA antagonist and kappa-opioid agonist discr iminative effects and that it may play a major role in mediating the discri minative stimulus effect of ibogaine. (C) 1999 American College of Neuropsy chopharmacology. Published by Elsevier Science Inc.