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Abstract

Mental illnesses like bipolar disorder and schizophrenia often present psychotic symptoms. Current antipsychotic medications, including clozapine, can cause serious side effects. This study investigates the potential therapeutic effects of the cholinesterase inhibitor donepezil compared to clozapine in a ketamine-induced psychosis model in rats. Forty adult male albino rats were divided into four groups: a control group, a psychosis group (given 25 mg/kg ketamine HCl for 14 days), a Clozapine + Psychosis group (received clozapine from days 8 to 21), and a Donepezil + Psychosis group (received donepezil during the same period). Neurobehavioral changes were assessed using the open field test, social interaction test, and Y-Maze test. After the study, the rats were euthanized for histological analysis, including GFAP immunohistochemistry and morphometric evaluation of the hippocampus. Ketamine induced positive, negative, and cognitive symptoms of psychosis and caused hippocampal degeneration, evident through cellular changes and increased GFAP expression. Both donepezil and clozapine mitigated these degenerative and behavioral symptoms associated with psychosis. The administration of ketamine resulted in psychotic symptoms and hippocampal degeneration in rats. Both clozapine and donepezil improved these outcomes, suggesting that donepezil may potentially substitute clozapine in treating ketamine-induced psychosis, addressing both clinical and histological issues effectively‎.

Keywords: Psychosis, Donepezil, Ketamine, Clozapine, Rat model Hippocampus

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