An experimental study in male wister rats: Impact of AILE in preventing ketamine induced spatial memory impairment in MWM and RAM

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Md. Enayet Ullah
Ripon Kumer Saha
Molua Jahan
Ujjol Chandra Dhar
Shams Ruhani Islam
Nadia Mahasinil Islam

Abstract

Background: Memory impairment involves a decline in cognitive functions such as memory, thinking, behavior, and the ability to perform daily tasks. The complex mechanisms underlying its pathogenesis contribute to the limited effectiveness of current treatments. Prolonged use of existing therapies often leads to reduced efficacy and serious side effects, complicating management. In this context, medicinal plants, particularly Azadirachta indica leaf extract (AILE), have gained attention due to their diverse therapeutic applications and minimal adverse effects. Objective: This study aimed to evaluate the effects of AILE on ketamine-induced memory impairment in male Wistar rats in Morris Water Maze (MWM) and Radial Arm Maze (RAM) tests. Methods: Ethical approval was obtained from the Institutional Review Board (IRB) of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. This experimental study was carried out in the Department of Physiology, BSMMU. The rats were divided into three groups: Group 1 (G1) normal memory, Group 2 (G2), memory impaired, Group 3 (G3) experimental. Each group was further divided into subgroups based on memory performance tests using the RAM and MWM. Data were expressed as mean±SEM and analyzed using SPSS (version 16). ANOVA with Bonferroni post hoc tests and Student’s paired t-tests were applied, with p ≤ 0.05 considered statistically significant. Results: Ketamine-treated rats demonstrated significantly increased working memory errors (p ≤ 0.001) and reference memory errors (p ≤ 0.001) in the RAM, along with delayed escape latency (p ≤ 0.001) and fewer target crossings (p ≤ 0.001) in the MWM compared to normal rats. Pretreatment with AILE significantly reduced working memory errors (p ≤ 0.001) and reference memory errors (p ≤ 0.001) in the RAM and improved escape latency (p ≤ 0.001) and target crossings (p ≤ 0.001) in the MWM relative to ketamine-treated rats. Notably, memory performance variables in AILE-pretreated rats were comparable to normal rats, except for a significantly higher frequency of target crossings (p ≤ 0.05) in the MWM. Conclusion: The results suggested that ketamine significantly impairs spatial learning and memory, as indicated by increased errors in the RAM and poorer performance in the MWM. However, pretreatment with AILE effectively mitigates these cognitive deficits, restoring memory performance to levels comparable to normal rats. Interestingly, AILE-pretreated rats demonstrated even greater target crossings in the MWM than normal rats, suggesting a potential enhancement of spatial memory retrieval. These findings indicate that AILE may have neuroprotective or cognitive-enhancing properties against ketamine-induced memory impairments. 

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