Abstract
Background: Aging process is often accompanied with some degree of decline in all the abilities, including learning and memory. One of the attracting research fields has been devoted to finding antiaging drugs. Metformin has shown some memory-enhancing features in aged humans and laboratory animals.

Aims and Objective: To evaluate the effects of 50, 75, and 100 mg/kg of metformin on the spatial memory performance of aged rats in the Morris water maze.

Materials and Methods: Thirty-two male 24-month-old rats were divided randomly into four groups (n = 8) including control group and 50-, 75-, and 100-mg/kg metformin groups. After 36 days of treatment, the learning process was assessed by the reference memory task in the Morris water maze. All the rats received water maze training (four trials/day for 5 days) to assess the hippocampal-dependent spatial learning and, then, received a 60-s probe trial test of spatial memory retention 24 h after the twentieth trial.

Result: Over 5 days of training, metformin (50, 75, and 100 mg/kg/day) treatment significantly reduced the latency and path length to find the escape platform (P < 0.01). In probe trials (without platform), on the last day of training, the metformin-treated groups spent significantly longer time in the platform quadrant when compared with the control group. Among the treated groups, 100 mg/kg dosage of metformin induced the best rehearsals memory (P < 0.05).

Conclusion: These results showed that, in the old rats, 36-day orally administered metformin showed a positive influence on the spatial memory performance in the Morris water maze.