自由行動下および睡眠中のラットの中枢・末梢に対するラメルテオンの効果

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  • Acute effect of ramelteon treatment on central andperipheral activity of rats during wakefulness and sleep

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<p>Sleep disorders adversely affect daily activities and lead to physiological andpsychiatric problems. The shortcomings of benzodiazepine hypnotics have led tothe development of ramelteon, one of melatonin MT1 and MT2 agonists. Althoughsleep-promoting effects of ramelteon have been documented, few studies haveprecisely investigated structure of sleep, neural oscillatory activities andperipheral effects.</p><p>In this study, we recorded electrocorticograms in the primary motor cortex, theprimary somatosensory cortex and the olfactory bulb, electrocardiograms, andelectromyograms of unrestrained rats treated with either ramelteon or vehicle.Neural-oscillation-based algorithm classified behavior of rats into threevigilance states (e.g., awake, rapid eye movement (REM) sleep, and non-REM(NREM) sleep). We demonstrated that ramelteon treatment promoted NREM sleep andenhanced fast gamma power in the primary motor cortex during NREM sleep, whileREM sleep was unaffected. As neocortical gamma oscillations locally coordinateneuronal firing, ramelteon may contribute to precise information processingduring sleep.</p><p>We further analyzed heartrate and its variability to evaluate effects oframelteon on cardiac function. We found ramelteon treatment significantlydecreased the standard deviation of R-R intervals during NREM sleep, but notduring REM sleep. As severe arrhythmia is related to sudden death, ramelteonwould not only promote sleep but also prevent cardiac irregularity.</p><p>Collectively, these results suggest that ramelteon ameliorates the quality ofsleep by modulating central neural activity and regularizing cardiacrhythms.</p>

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