Melatonin does not produce sedation in rats: A chronobiological study

Background: Melatonin has been associated with a wide variety of cellular, neuroendocrine, and neurophysiological processes. Clinical studies have reported the use of melatonin as an agent that exerts sedative-hypnotic effects. However, evidence of the sedative-hypnotic effects of different doses of melatonin is inconsistent, and available data regarding its night/day-time sedative effects are limited. The purpose of this study was to evaluate the effects of melatonin administered at different times of day on the magnitude of the sedative-hypnotic activity of different melatonin doses (5, 10, 30, and 50 mg/kg) in rats. Methods: Sedation was assessed in Wistar rats behaviorally, using rota-rod, spontaneous locomotor activity, and fixed-bar tests at different times of day (ZT4, ZT10, ZT16, and ZT22). Results: Our results showed that, compared to trazodone, acute and chronic dosing of <= 5 mg melatonin produced mild, transient sedative effects, mainly in the light period. Nevertheless, doses of >= 10 mg/kg did not cause sustained sedative effects. Conclusion: These results suggest that melatonin may be used for sedation induction, mainly in preoperative patients.