Metformin ameliorates learning and memory deficits in streptozotocin-induced diabetic rats

Document Type : Research Paper


1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Neurophysiology Research Center, Shahed University, Tehran, Iran


Background and Objective: Diabetes mellitus (DM) in long-term is associated with learning and memory decline. Metformin is an anti-diabetic drug with antioxidant and memory-improving effects. Thus, this research study was conducted to assess the effect of metformin on learning and memory in diabetic rats.
Materials and Methods: In the present study, male Wistar rats (n=32) were randomly assigned to 4 groups: control, control treated with metformin (200 mg/kg), diabetic, and diabetic treated with metformin (200 mg/kg). Diabetes was induced by streptozotocin (STZ) at a dose of 60 mg/kg. Metformin was administered i.p. at a dose of 200 mg/kg one week after STZ injection for 7 weeks. Blood sample was taken from retro-orbital plexus before STZ injection and 4 and 8 weeks after STZ injection to measure blood glucose level. Passive avoidance and Y maze tests were performed to evaluate learning and memory dysfunctions.
Results: After 8 weeks, diabetic rats showed a significant cognitive decline in passive avoidance and Y maze tests that was significantly improved after metformin treatment. In addition, metformin exerted a significant hypoglycemic effect in this model of DM.
Conclusion: This study clearly showed that treatment with metformin for 7 weeks could ameliorate cognitive decline in diabetic animals and part of its beneficial effect is due to its hypoglycemic effect.


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