ETHNOPHARMACOLOGICAL RELEVANCE:Erythrophleum ivorense (A Chev.) is a common plant in the tropics. Its use as ordeal poison in folklore medicine is controversial. The incoordination and behavioral changes following consumption are often associated with guilt. This study is aimed at dispelling or upholding this belief by investigating the actions of E. ivorense on the brain and behavior using rat model. MATERIALS AND METHODS:Sixty male Wistar rats were equally divided into five groups; control group received distilled water, test groups were administered 10, 20, 30 and 40 mg/kg ethanolic extract of E. ivorense in a daily oral dose for 28 days. Cognition (Morris water maze) depression (forced swim test), motor function (hanging wire and inverted wire mesh grid grip tests) and exploratory assessments were done. Brains were stained with H&E, Cresyl violet and immunohistochemistry was done using GFAP, anticalbindin-D28k, Iba-1 and MBP antibodies. RESULTS:At all doses, E. ivorense significantly (P ≤ 0.05) increased escape latency in the Morris water maze compared to control. Forced swim test showed a dose-related increase in duration of immobility, significant reduction in hanging latency in hanging wire and wire mesh grid grip test was also observed. Depletion of Purkinje cells of the cerebellum and hippocampal neurons was observed with H&E and cresyl violet. Immuno-staining revealed astrocytic activation in the cerebellum, loss of dendritic spines, cortical microglial activation and demyelination in the cerebellum and dentate gyrus of the hippocampus. CONCLUSION:The ethanolic extract of E. ivorense stem bark caused a dose-dependent deficit in learning, memory and motor coordination with evidences of depression in rats. It is concluded that the plant is neurotoxic and induce several neurobehavioral changes.