Objective: We investigated the anti-amnesic and cognitive enhancing effects of the ethanol leaf extract of Milicia excelsa in mice. Methodology: Amnesia was induced by intraperitoneal injection of scopolamine (0.4mg/kg) in Morris Water Maze; scopolamine (1mg/kg) on Y-maze test; scopolamine (0.4mg/kg) and diazepam (1mg/kg) on elevated plus maze. The effect of the extract on learning and memory of young and aged mice was also investigated on the elevated plus maze. The probable mechanism of cognitive enhancing effects of the extract was investigated using acetylcholinesterase enzyme and nitric oxide assays. Results: The extract significantly (p<0.05) attenuated amnesia induced by scopolamine in Morris water maze; reversed amnesia induced by scopolamine and diazepam on elevated plus maze; increased spontaneous alternation behaviour without modifying locomotor activities on Y-maze test; inhibited natural age-induced learning and memory impairment of aged mice while the learning and memory of young mice were significantly (p<0.05) enhanced on elevated plus maze. The extract also significantly (p<0.05) reduced acetylcholinesterase enzyme activity and increased nitric oxide concentration in the mice whole brain. Conclusion: This study, therefore, concluded that ethanol leaf extract of Milicia excelsa may possess anti-amnesic and memory enhancing effects which may involve cholinergic and nitergic pathways.
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