Role of Azadirachta indica leaf extract on Working and Reference Memory of ketamine Induced Memory Impaired Male Wistar Rats in Morris Water Maze

Abstract

Background: Ketamine, a known NMDA receptor antagonist, induces memory impairment in experimental models. Azadirachta indica leaf extract (AILE), rich in bioactive compounds, has shown potential neuroprotective effects. This study evaluates the effects of AILE on ketamine induced memory impairment using the Morris Water Maze (MWM) test in male Wistar rats. Methods & Materials: This experimental study aimed to investigate the effects of AILE on working and reference memory in ketamine-induced memory-impaired male Wistar rats. 24 rats were selected for the animal selection. Male wistar rats were divided into normal memory (oral normal saline treated,5ml/kg/day for 26 days), memory impaired (intraperitoneal ketamine treated, 15mg/kg/day during 5 days of acquisition phases) and experimental (oral AILE treated, 300mg/kg/day for 26 days and intraperitoneal ketamine, 15mg/kg/day during 5 days of acquisition phases). The study was conducted at the Memory Laboratory, Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), duration from March 2020 to February 2021. Ethical approval was obtained following a thorough review by Institutional Review Board (IRB) of BSMMU. Results: Ketamine administration significantly impaired spatial working and reference memory, evidenced by increased escape latency and reduced target crossings. AILE co-administration significantly improved these parameters, reducing escape latency and increasing target crossings. Remarkably, AILE enhanced reference memory retrieval beyond normal levels, indicating its therapeutic potential. Conclusion: AILE mitigates ketamine-induced memory deficits and enhances spatial memory retrieval, likely through NMDA receptor modulation, oxidative stress reduction, and apoptotic pathway attenuation. These findings highlight the potential of AILE as a therapeutic agent for memory impairment disorders.