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Background: Alzheimer Disease (AD) is an age-related neurodegenerative disorder with a progressive impairment of cognitive function. The pineal gland hormone melatonin (MEL) has been known as a protection agent against AD. However, the effect of melatonin in various doses is inconsistent. Objectives: In this study, we aimed to investigate two doses of MEL on learning and memory in the amyloid-βeta (Aβ)-induced AD in the rats. Materials &amp; Methods: Forty-eight male Wistar rats were used in the experiment and randomly divided control, sham, vehicle, AD, AD+MEL10 mg/kg, and AD+MEL 20 mg/kg groups. Intracerebroventricular injection of Aβ1–42 was used to develop the animal model of AD. Also, MEL-treated groups received an intraperitoneal injection of MEL for 4 next weeks. The Morris Water Maze (MWM) and Passive Avoidance Learning (PAL) tests were used to examine animals’ learning and memory. The brain of animals was removed for immunohistochemistry for anti- Amyloid Precursor Protein (APP). Results: Intra-peritoneal injection of MEL significantly improve learning and memory in MWM (P=0.000) and PAL test (P=0.000), but there were no significant changes in the two groups that received the melatonin (P&gt;0.05). Histopathological analysis revealed that the clearance of APP deposition in the AD+MEL20 group was considerable compared with the AD+MEL10 group (P=0.000). Conclusion: Our findings indicate that 10 and 20 mg/kg doses of melatonin have similar results on learning and memory in the AD model. But 20 mg/kg of melatonin has significantly more effect on the clearance of APP deposition.

The Effect of Different Doses of Melatonin on Learning and Memory Deficit in Alzheimer Model of Rats