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Background & objectives: Epidemiological Studies have shown that diabetes increase the risk of developing Alzheimer’s disease (AD).also several studies have confirmed that long term use of Metformin (Met) improves cognitive function in diabetic patients. The aim of the present study was to investigate the effects of Met on learning and memory in diabetic and non-diabetic rats. Methods: Animals were divided into 2 groups including healthy and diabetic group. In healthy group, normal rats subdivided into control, saline and Met groups which received saline or Met (500mg/kg) and in diabetic group including DM, DM+saline and DM+Met subgroups, diabetic rats received saline or Met (100, and 200mg/kg) for 20 days. Diabetes was induced by intraperitoneal injection (ip) of streptozotocin (STZ). Results: Our results showed that Met (500mg/kg, ip) impaired spatial learning but improved spatial memory in normal rats. The results also showed that Met improved learning and memory in diabetic rats in a dose dependent manner, so that the rats of DM+Met group compared to DM+saline group found platform in less time and with less distance traveled. Met also increased the percentage of time elapsed and the distance swum in the target quadrant in diabetic rats during the probe trial. Conclusion: An intraperitoneal injection of STZ resulted in a significant decline in learning and memory and treatment with Met can enhance learning and memory in a dose dependent manner, therefore, it is useful for treatment of cognitive impairment in diabetic patients.

The Effect of Different Doses of Metformin on Spatial Learning and Memory in Diabetic Rats