A dose-response study of Ibogaine-induced neuropathology in the rat cerebellum

Ibogaine (IBO) is an indole alkaloid from the West African shrub, Tabernant he iboga. It is structurally related to harmaline, and both these compounds are rigid analogs of melatonin. IBO has both psychoactive and stimulant pr operties. In single-blind trials with humans, it ameliorated withdrawal sym ptoms and interrupted the addiction process. However, IBO also produced neu rodegeneration of Purkinje cells and gliosis of Bergmann astrocytes in the cerebella of rats given even a single dose (100 mg/kg, ip). Here, we treate d rats (n = 6 per group) with either a single ip injection of saline or wit h 25 mg/kg, 50 mg/kg, 75 mg/kg, or 100 mg/kg of IBO. As biomarkers of cereb ellar neurotoxicity, we specifically labeled degenerating neurons and axons with silver, astrocytes with antisera to glial fibrillary acidic protein ( GFAP), and Purkinje neurons with antisera to calbindin, All rats of the 100 -mg/kg group showed the same pattern of cerebellar damage previously descri bed: multiple bands of degenerating Purkinje neurons. All rats of the 75-mg / kg group had neurodegeneration similar to the 100-mg/kg group, but the ba nds appeared to be narrower. Only 2 of 6 rats that received 50 mg/kg were a ffected; despite few degenerating neuronal perikarya, cerebella from these rats did contain patches of astrocytosis similar to those observed with 75 or 100 mg/kg IBO. These observations affirm the usefulness of GFAP immunohi stochemistry as a sensitive biomarker of neurotoxicity. None of the section s from the 25-mg/kg rats, however stained, were distinguishable from saline controls, indicating that this dose level may be considered as a no-observ able-adverse-effect level (NOAEL).