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Neurobehavioural, Biochemical and Histological Effects of Metformin in a Scopolamine-Induced Cognitive Impairment Model in Male Wistar Rats

Onyinye Mmoto, Adejoke Y. Onaolapo, Olakunle J. Onaolapo

2026

10 participants

Abstract

Alzheimer’s disease (AD) causes progressive memory loss and cognitive decline. Current treatments, including donepezil, provide mainly symptomatic relief, prompting interest in drug repurposing. Metformin, an antidiabetic drug, has demonstrated promising neuroprotective effects beyond glycaemic control. The present study assessed the effects of metformin on behavioural, systemic biochemical, and histological alterations in a scopolamine-induced cognitive impairment model in male Wistar rats. Fifty rats weighing 200–240 g were randomly assigned to five groups (n=10). Group A received normal saline and distilled water; Group B received scopolamine (1 mg/kg); Group C received scopolamine (1 mg/kg) and donepezil (3 mg/kg); Groups D and E received scopolamine (1 mg/kg) with metformin at 100 and 200 mg/kg, respectively. Scopolamine was administered intraperitoneally for 7 days, while metformin, donepezil, and vehicle treatments were administered orally for 21 days. Behavioural assessments were conducted on day 28. Scopolamine administration was associated with alterations in behavioural performance, systemic biochemical indices, and neuronal morphology. Metformin treatment was associated with improvements in locomotor activity, spatial working memory, and recognition memory. Serum biochemical analyses demonstrated treatment-related alterations in malondialdehyde, total antioxidant capacity, tumour necrosis factor-α, interleukin-1β, interleukin-10, and acetylcholinesterase activity…

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