NEUROENDOCRINE AND NEUROCHEMICAL EFFECTS OF ACUTE IBOGAINE ADMINISTRATION - A TIME-COURSE EVALUATION

Ibogaine (IBO) is an indole alkaloid that is reported to facilitate dr ug abstinence in substance abusers. Despite considerable investigation , the mechanism of IBO action in vivo and its suitability as a treatme nt for drug addiction remains unclear. The present study was designed to evaluate the time-course effects of acute IBO on neuroendocrine and neurochemical indices. Adult male rats were treated with i.p. saline or 50 mg/kg IBO and sacrificed 15: 30, 60, 120 min and 24 h later. Tru nk blood was collected for hormone measures and brains were dissected for neurochemical analyses. IBO produced a rapid elevation in plasma p rolactin that declined to control levels by 60 min. Corticosterone lev els increased 15 min after drug administration, continued to increase for 120 min, but returned to control levels 24 h after dosing. IBO dec reased dopamine (DA) concentrations in the striatum and frontal cortex at 30, 60 and 120 min after injection while DA metabolites, 3,4-dihyd roxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were elevat ed over the same time period. 24 h after IBO, DOPAC concentrations in striatum and HVA levels in the frontal cortex were below control value s. Serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5- HIAA) were decreased at 60 min after IBO administration only in the st riatum. These data indicate that a single injection of IBO produces a spectrum of effects that includes: (I) elevation of plasma prolactin a nd corticosterone, (2) short- and long-term effects on DA neurotransmi ssion, and (3) modest, transient effects of 5-HT neurotransmission. Th e effects of IBO reported herein may have relevance to the anti-addict ive properties of this drug, and this proposal warrants further invest igation.