Effects of memantine and donepezil on social memory, anxiety-like behavior and the expression levels of microRNA-124, microRNA-125b, and microRNA-132 in scopolamine-induced memory impairment in rats.

Introduction: Almost all physiological processes are modulated by microRNAs, therefore, dysregulation of these small regulatory RNAs is observed in a variety of diseases, including cognitive impairments.

Methods: In this study, 40 male Wistar rats were randomly divided into five groups of control, scopolamine, donepezil, memantine, and combined administration of donepezil + memantine. Rats in scopolamine, donepezil, memantine, and combined administration of donepezil + memantine groups received scopolamine (1 mg/kg-intraperitoneal) for 7 days. After the last administration of scopolamine, was started injecting donepezil (3 mg/kg-i.p.), memantine (10 mg/kg-i.p.), and combined administration of Donepezil + Memantine (0.5 mg/kg and 5 mg/kg-i.p., respectively), up to 21 days. Twenty-four hours after the last injection, elevated plus-maze, social interaction, open field tests, and gene expression analysis of miR-124, miR-125b, and miR-132 in the hippocampus were carried out.

Results: The results of the behavioral tests indicate that donepezil and memantine significantly prevented Scopolamine-induced anxiety, sociability, and social memory decline. The gene expression of selected microRNAs did not significantly differ between the groups.

Discussion: This study revealed that donepezil and memantine effectively prevent synaptic plasticity disruption and cognitive decline induced by scopolamine. Findings indicated that this treatment is unrelated to the expression of the selected microRNAs. The positive effects of memantine and donepezil depend on age, dosages, cognitive task demands, and possibly the length and timing of the treatment.