Assessment of Neuroprotective and Memory-Enhancing Activity of Donepezil Against Scopolamine-Induced Cognitive Impairment in Wistar Rats

Registration ID: IJNRD_326903

Published ID: IJNRD2607083

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Tejas Manoharrao Narsinge, Dr. Nikhil N. Jadhav

Donepezil; scopolamine; cognitive impairment; neuroprotection; acetylcholinesterase; oxidative stress; Wistar rats

Background: Cholinergic deficiency and oxidative stress are central to the cognitive decline observed in Alzheimer's disease (AD), and preclinical characterisation of acetylcholinesterase (AChE) inhibitors against these mechanisms remains valuable for validating their neuroprotective potential beyond symptomatic cholinergic enhancement. Objective: This study evaluated the memory-enhancing and neuroprotective activity of donepezil, administered at three oral dose levels, against scopolamine-induced cognitive impairment in adult male Wistar rats, using behavioural, biochemical and histopathological endpoints. Methods: Thirty adult male Wistar rats (180–200 g) were allocated to five groups (n = 6): normal control, scopolamine (3 mg/kg, i.p.) disease control, and three scopolamine-challenged groups pre-treated with oral donepezil at 1, 2 or 3 mg/kg for 21 consecutive days. Spatial learning and reference memory were assessed using the Morris water maze (MWM), retention memory using the elevated plus maze (EPM), and aversive memory using the passive avoidance (PA) paradigm. Brain AChE activity and oxidative stress indices (malondialdehyde [MDA], reduced glutathione [GSH], superoxide dismutase [SOD] and catalase) were quantified, and hippocampal CA1 cytoarchitecture was examined on haematoxylin and eosin (H&E)-stained sections using a semi-quantitative injury score. Results: Scopolamine significantly prolonged MWM escape latency and impaired PA/EPM retention, reduced target-quadrant time, elevated brain AChE activity and MDA, depleted GSH, SOD and catalase, and produced marked CA1 neuronal degeneration, oedema and pyknosis relative to normal controls (p < 0.001 for all measures). Donepezil produced a dosedependent reversal of every deficit; the standard-dose group (3 mg/kg) consistently approached normal-control values and was statistically non-significant versus normal control on several endpoints, while remaining significantly different from disease control (p < 0.001). Conclusion: Donepezil conferred significant memory-enhancing and neuroprotective effects in the scopolamine model, an action attributable to combined augmentation of cholinergic transmission and attenuation of oxidative stress, with structural preservation of hippocampal CA1 neurons corroborating the behavioural and biochemical findings.

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Tejas Manoharrao Narsinge & Dr. Nikhil N. Jadhav (July-2026). Assessment of Neuroprotective and Memory-Enhancing Activity of Donepezil Against Scopolamine-Induced Cognitive Impairment in Wistar Rats . INTERNATIONAL JOURNAL OF NOVEL RESEARCH AND DEVELOPMENT, 11(7), a831-a845. https://ijnrd.org/papers/IJNRD2607083.pdf

Volume 11 Issue 7, July-2026

Pages : a831-a845

Paper Reg. ID: IJNRD_326903

Published Paper Id: IJNRD2607083

Research Area: Pharmacy All

Author Type: Indian Author

Country: Beed, Maharashtra, India

Published Paper PDF: https://ijnrd.org/papers/IJNRD2607083.pdf

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