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BACKGROUND: Sleep deprivation cannot only cause learning and memory impairment of animal and human, but also lead to increased content of nitric oxide in brain tissue of rats. Melatonin has the effects of antifreeradical and antioxidation. It has been reported that melatonin can improve aluminum chloride and morphine abstinence induced learning and memory impairment of animal, however, whether it has influence on sleep deprivation induced learning and memory impairment is not very clear. OBJECTIVE: To observe the effect of melatonin on memory of rats after sleep deprivation and analyze its possible mechanism. DESIGN: Randomized controlled trial.SETTING: Teaching and Experiment Center of Basic Medicine and Department of Nursing, the Fourth Military Medical University.MATERIALS: The experiment was performed in Teaching and Experiment Center of Basic Medicine of the Fourth Military Medical University in January 2005. A total of 24 adult male Sprague Dawley rats were selected and randomly divided into 3 groups, namely, control group, small dosage of melatonin group and large dosage of melatonin group, with 8 in each group on the basis of random digits table.METHODS: To rats in small dosage of melatonin group and large dosage of melatonin group, the dosage of melatonin was 5 mg/kg and 15 mg/kg respectively, which was made into 2 mL solution and intraperitoneally injected into the rats at 17:00 o'clock every day, while rats in control group were injected with 2 mL physiological sodium at the same time, once a day for continuous 7 days. Then a 3-day sleep deprivation was given to the rats; melatonin or physiological sodium were also given according to different groups during these days. Rat model of sleep deprivation was established by "Flower Ppot" technique; water maze was used for detecting the memory of rats after 48-hour and 72-hour sleep deprivation; took escape latency (s) as indicator of changes of learning and memory of rats; the shorter the escape latency, the better the spacial memory of rats. When sleep deprivation was finished, all the rats were put to death and hippocampus and cerebral cortex were taken out in ice bath. The content of nitric oxide in cerebral cortex and hippocampus was detected with the method of nitrate reduction, and malondialdehyde (MDA) with the method of thiobarbital acid.MAIN OUTCOME MEASURES: Results of escape latency after 48hour and 72-hour sleep deprivation. Contents of nitric oxide and MDA in cerebral cortex and hippocampus of rats.There was significant difference in escape latency in water maze after 48-hour and 72-hour sleep deprivation among each group (F=11.886, P=0.000)and (F=5.440, P=0.012); the escape latency after 48-hour and 72-hour sleep deprivation remarkably decreased both in small and large dosage of melatonin groups as compared with control group, and the latency after 48-hour sleep deprivation was shorter in large dosage group than that in small ide and MDA in brain of rats among each group, namely, nitric oxide in cerebral cortex (F=14.038, P=0.000), MDA in cerebral cortex (F=27.414,P=0.000), nitric oxide in hippocampus (F=22.692, P=0.000), MDA in hippocampus (F=14.316, P=0.000). Compared with control group, the contents of nitric oxide and MDA in cerebral cortex and hippocampus in the two experimental groups decreased significantly, and there was obvious difference in the content of nitric oxide in hippocampus between large and small dosage groups, which showed a dose-effect relationship.CONCLUSION: Melatonin can improve memory impairment of rats after sleep deprivation, which may be closely related to the effect of inhibiting the increase of nitric oxide and MDA in their cerebral cortex and hippocampus.