Objective: Herein, we aimed to investigate the long-term effects of neonatal hypoxia and the potential protective role of Melatonin (MLT) and Memantine (MEM) on the learning and memory.
Methods: Seven-day-old rat underwent right carotid ligation, followed by hypoxia. Rat received MLT (4 mg/kg), MEM (20 mg/kg), and MLT+MEM combination after hypoxia. We tested these rats for anxiety by elevated O-maze and for spatial learning and memory by Morris water maze (MWM) at postnatal day 45.
Results: Hypoxia increased the level of anxiety compared to the control group (P= 0.05) while treatment of MLT, MEM, and MLT+MEM ameliorated this effect. In addition, hypoxia produced significant decrease in spatial learning of the rats on the fourth day of training (P≤ 0.05) and the percent time spent in the platform quadrant and the entrance frequencies to the platform quadrant compared to the control group (P= 0.049 and P= 0.023). Treatment of MLT, MEM, and MLT+MEM after hypoxia improved the performance of the rats at the third (P= 0.686, P= 0.876, P= 0.977, respectively) and fourth day (P= 0.738, P=0.553, P= 0.789, respectively) of MWM training. The decrease in the percent time spent was ameliorated by the treatment of MLT (P= 0.239), MEM (P= 0.289), and MLT+MEM (P= 0.567) compared to the control group. In addition, MLT treatment significantly increased the entrance frequency to the platform quadrant compared to the hypoxia group (P= 0.020).
Conclusion: Our data suggested that the MLT was more effective in the release of memory deficits from hypoxia-related damage. MLT might have a therapeutic value in improving hypoxic damage in the developing brain.
Key words: Neonatal Hypoxia; Learning; Memory; Melatonin; Memantine; Morris Water Maze
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