Dose-dependent effects of vildagliptin (DPP-4 inhibitor) in a scopolamine-induced memory impairment model in rats

Cognitive decline and dementia are closely linked with metabolic disorders such as type 2 diabetes mellitus, sharing common pathophysiological mechanisms including insulin resistance, inflammation, and oxidative stress. This study investigated the neuroprotective potential of vildagliptin, an antidiabetic medication, in a rat model of scopolamine-induced acute memory impairment, focusing on its effects on learning and memory as well as its association with cholinergic activity, inflammatory responses, and lipid peroxidation as an indicator of oxidative stress.

Male Wistar Albino rats were orally administered vildagliptin (0.5, 5, or 50 mg/kg/day) or physiological saline for 4 weeks. Spatial learning and memory were assessed using the Morris water maze (MWM) test. Memory impairment was induced by intraperitoneal injection of scopolamine (1 mg/kg, i.p.) before the probe trial of the MWM. Following behavioral testing, rats were sacrificed, and hippocampal tissues were isolated for biochemical analysis.

Vildagliptin significantly enhanced spatial learning performance in a dose-dependent manner during the acquisition phase of the MWM. Scopolamine administration markedly impaired memory performance in rats. Pretreatment with vildagliptin at all tested doses prevented these memory deficits during the MWM probe trial. In addition, vildagliptin robustly prevented scopolamine-induced increases in hippocampal acetylcholinesterase (AChE) activity and elevated levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA).

These findings suggest that vildagliptin may exert protective effects against cognitive impairment by modulating cholinergic activity, inflammatory responses, and lipid peroxidation.