Noribogaine generalization to the ibogaine stimulus: correlation with noribogaine concentration in rat brain.
C Zubaran, M Shoaib, I P Stolerman, John Pablo, Deborah C. Mash
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology July 1, 1999 DOI: 10.1016/s0893-133x(99)00003-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ibogaine Noribogaine Dizocilpine U50 488 |
| Dose | 10 mg/kg i.p. ibogaine, 0.08 mg/kg i.p. dizocilpine, 5 mg/kg i.p. U50,488 |
| Topics | Ibogaine |
| Keywords | Psychoactive compound Alkaloid Drug metabolite Neuropharmacology Brain responses Drug action Psychopharmacology Stimulus effects Drug metabolism Biotransformation Animal studies Preclinical research Rat model |
| Citations | 31 |
| Key points | The metabolite noribogaine appears to mediate the discriminative stimulus effect of ibogaine in rats, likely without NMDA antagonist or kappa-opioid agonist properties. |
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.