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Background: Chronic diabetes mellitus is accompanied with disturbances in learning, memory, and cognitive skills. Noticing the existing evidence regarding the anti-diabetic potential of hesperetin, the effect of its chronic administration on learning and memory in diabetic rats was investigated. Materials and Methods: In this experimental study, 40 male Wistar rats were divided into control, hesperetin-treated control, diabetic, and hesperetin/glibenclamide-treated diabetic groups. For evaluation of learning and memory, initial (IL) and step-through latencies (STL) were determined at the end of the study using passive avoidance test, and the alternation behavior percentage was obtained using Y maze. Results: STL significantly decreased in the diabetic (p<0.01) and hesperetin-treated diabetic (p<0.05) groups in comparison to the control group however, the difference between these two groups was not significant. Alternation percentage in the diabetic group was significantly lower in comparison to the control group (p<0.05), but the hesperetin-treated diabetic group revealed a significant difference in comparison to the diabetic group (p<0.05). Conclusion: Although long-term treatment with hesperetin does not enhance the capability of retention and recall in diabetic animals on the passive avoidance test, it can improve the short-term spatial memory in diabetic animals.

Keywords: Diabetes mellitus, Hesperetin, Learning, Memory

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