Ramelteon modulates gamma oscillations in the rat primary motor cortex during non-REM sleep

J Pharmacol Sci. 2021 Jan;145(1):97-104. doi: 10.1016/j.jphs.2020.11.006. Epub 2020 Nov 20.


Sleep disorders adversely affect daily activities and cause physiological and psychiatric problems. The shortcomings of benzodiazepine hypnotics have led to the development of ramelteon, a melatonin MT1 and MT2 agonist. Although the sleep-promoting effects of ramelteon have been documented, few studies have precisely investigated the structure of sleep and neural oscillatory activities. In this study, we recorded electrocorticograms in the primary motor cortex, the primary somatosensory cortex and the olfactory bulb as well as electromyograms in unrestrained rats treated with either ramelteon or vehicle. A neural-oscillation-based algorithm was used to classify the behavior of the rats into three vigilance states (e.g., awake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep). Moreover, we investigated the region-, frequency- and state-specific modulation of extracellular oscillations in the ramelteon-treated rats. We demonstrated that in contrast to benzodiazepine treatment, ramelteon treatment promoted NREM sleep and enhanced fast gamma power in the primary motor cortex during NREM sleep, while REM sleep was unaffected. Gamma oscillations locally coordinate neuronal firing, and thus, ramelteon modulates neural oscillations in sleep states in a unique manner and may contribute to off-line information processing during sleep.

Keywords: Electrocorticogram; Gamma oscillation; Ramelteon; Rat; Sleep.

MeSH terms

  • Animals
  • Electrocorticography
  • Gamma Rhythm / drug effects*
  • Indenes / pharmacology*
  • Male
  • Motor Cortex / physiology*
  • Rats
  • Rats, Wistar
  • Receptor, Melatonin, MT1 / agonists
  • Receptor, Melatonin, MT2 / agonists
  • Sleep, REM / drug effects*
  • Sleep, REM / physiology*


  • Indenes
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • ramelteon