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

Onyinye Theresa MMOTO, Boluwatife Mary OLADIPUPO, Adejoke Yetunde ONAOLAPO, Olakunle James ONAOLAPO

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 relative to the scopolamine group. Histological examination showed preservation of neuronal architecture in the prefrontal cortex and CA1 region of the hippocampus following metformin treatment. Overall, metformin attenuated selected behavioural, systemic biochemical, and histological alterations associated with scopolamine-induced cognitive impairment. These findings support further investigation of metformin in experimental models of cognitive dysfunction.

KEYWORDS: Scopolamine, Metformin, Donepezil, Cognitive Impairment, Neurodegeneration