Acute and chronic administration of ibogaine to the rat results in astrogliosis that is not confined to the cerebellar vermis.

High doses of ibogaine, a psychoactive alkaloid, damage brain regions beyond the cerebellum in rats, with effects depending on sex and dosage. Single doses caused dose-related increases in GFAP, a marker of brain cell injury, across multiple brain areas in both sexes. Repeated doses led to large GFAP increases (up to 200% of control) in the hippocampus, olfactory bulbs, brain stem, and striatum of female rats but not males. In the hippocampus of chronically treated females, other structural proteins also increased, suggesting a sprouting response to damage. The findings indicate that ibogaine's neurotoxic effects are not limited to the cerebellum and vary by sex and dosing schedule.

Study at a glance

Abstract

Acute administration of high doses of ibogaine (IBG) to the male rat results in degeneration of Purkinje cells and reactive gliosis in the cerebellar vermis. We examined whether acute and chronic administration of IBG to male and female rats results in gliosis as determined by quantification of the astroglial intermediate filament protein, glial fibrillary acidic protein (GFAP). After acute administration of IBG, rats of both sexes showed dose-related increases in GFAP that were not confined to the cerebellar vermis. After chronic administration of IBG, female, but not male rats, showed large (as much as 200% of control), dose-related increases in GFAP in hippocampus, olfactory bulbs, brain stem and striatum, but not cerebellum. In hippocampus, the cytoskeletal proteins, neurofilament 68 (NF-68) and beta-tubulin were increased in females treated chronically with IBG, findings consistent with a damage-induced sprouting response. Together, the data indicate that IBG damages areas of the brain outside the cerebellum and that the sites damaged are dependent on sex and dosage regimen.