Background: The methylprednisolone (MP) is a synthetic glucocorticoid steroid initially developed for its enhanced anti-inflammatory activity. The present study aimed to examine the effect of MP on the spatial learning and memory in an experimental model of Alzheimer’s disease in rats.

Materials and Methods: Male rats were allocated into five groups: control group lesion group which received electrically-induced lesion (0.5 mA, 3s) in the nucleus basalis magnocellularis (NBM) to create Alzheimer’s model sham group (the electrode was impaled into the NBM with no lesion) MP group (lesion+30 mg/kg MP) and saline group (lesion NBM + 0.2 mL saline). After one week, the rats were trained to perform the Y-maze task for five days. The animals were tested for spatial memory one month later.

Results: Results showed that the bilateral lesion of NBM impaired the spatial learning compared to the control group (P<0.01). The administration of MP significantly improved spatial learning of rats with the Alzheimer’s disease (P<0.001). Moreover, no effect on spatial learning was seen in the sham group compared with the lesion group. No significant difference was observed between the results in the 5th day of training and the memory test after one month.

Conclusion: Administration of MP can be an effective treatment for the Alzheimer’s disease.