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

In rats trained to distinguish ibogaine from a placebo, the metabolite noribogaine produced the same discriminative effect as ibogaine but at roughly half the dose. Noribogaine was found in blood and brain tissue after either ibogaine or noribogaine was given. At doses that produced the discriminative effect, noribogaine concentrations in plasma, cerebral cortex, and striatum were similar whether ibogaine or noribogaine was administered. The findings suggest noribogaine may lack the NMDA antagonist and kappa-opioid agonist effects of ibogaine and may be primarily responsible for ibogaine's discriminative stimulus effect in rats.

Study at a glance

Abstract

The discriminative stimulus effects of ibogaine and noribogaine in rats have been examined in relation to their concentrations in blood plasma and brain regions and to receptor systems through which they have been proposed to act. Rats were trained to discriminate ibogaine (10 mg/kg i.p.), the NMDA antagonist dizocilpine (0.08 mg/kg i.p.) or the kappa-opioid agonist U50,488 (5 mg/kg i.p.) from vehicle in a standard two-lever operant conditioning procedure with a tandem VI-FR schedule of food reinforcement. Only rats trained on ibogaine generalized to noribogaine, which was approximately twice as potent as the parent compound. Noribogaine was detected in plasma and brain after administration of ibogaine and noribogaine. At the ED50 doses for the discriminative 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 discriminative effects and that it may play a major role in mediating the discriminative stimulus effect of ibogaine.