Acute Ramelteon Treatment Maintains the Cardiac Rhythms of Rats during Non-REM Sleep

Biol Pharm Bull. 2021;44(6):789-797. doi: 10.1248/bpb.b20-00932.


Sleep curtailment negatively affects cardiac activities and thus should be ameliorated by pharmacological methods. One of the therapeutic targets is melatonin receptors, which tune circadian rhythms. Ramelteon, a melatonin MT1/MT2 receptor agonist, has recently been developed to modulate sleep-wake rhythms. To date, the sleep-promoting effect of ramelteon has been widely delineated, but whether ramelteon treatment physiologically influences cardiac function is not well understood. To address this question, we recorded electrocardiograms, electromyograms, and electrocorticograms in the frontal cortex and the olfactory bulb of unrestrained rats treated with either ramelteon or vehicle. We detected vigilance states based on physiological measurements and analyzed cardiac and muscular activities. We found that during non-rapid eye movement (non-REM) sleep, heartrate variability was maintained by ramelteon treatment. Analysis of the electromyograms confirmed that neither microarousal during non-REM sleep nor the occupancy of phasic periods during REM sleep was altered by ramelteon. Our results indicate that ramelteon has a remedial effect on cardiac activity by keeping the heartrate variability and may reduce cardiac dysfunction during sleep.

Keywords: electrocardiogram; heartrate variability; ramelteon; rat; sleep.

MeSH terms

  • Animals
  • Electrocardiography
  • Electrocorticography
  • Electromyography
  • Frontal Lobe / drug effects
  • Frontal Lobe / physiology
  • Heart Rate / drug effects*
  • Indenes / pharmacology*
  • Male
  • Olfactory Bulb / drug effects
  • Olfactory Bulb / physiology
  • Rats, Wistar
  • Sleep, REM / drug effects*
  • Sleep, REM / physiology


  • Indenes
  • ramelteon