Rapid phase advance of the 24-h melatonin profile in response to afternoon dark exposure

Am J Physiol. 1998 Jul;275(1):E48-54. doi: 10.1152/ajpendo.1998.275.1.E48.


To investigate the adaptation of melatonin secretion to an abrupt time shift and the effects of sleep facilitation with a hypnotic, eight subjects were submitted to an 8-h advance shift achieved by advancing bedtimes from 2300-0700 to 1500-2300. Each subject participated in two studies (i.e., placebo and zolpidem). Each study included a baseline period with dim light during waking hours and 2300-0700 bedtimes in total darkness. Blood samples for determination of plasma melatonin were obtained at 20-min intervals for 68 h. Advanced exposure to sleep and darkness resulted in a nearly 2-h advance of melatonin onset, which appeared within 6 h after lights-out during the first shifted night, and an almost 1-h advance of the melatonin offset. No further adaptation occurred during the second shifted sleep period. Zolpidem had no beneficial effects on the adaptation of the melatonin profile. There was no relationship between sleep parameters and the magnitude of the melatonin shifts. Thus the overall advance of melatonin profiles was primarily achieved during the initial exposure to an 8-h period of darkness. The present data suggest that exposure to dark affects human circadian phase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Darkness
  • Female
  • Humans
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Melatonin / blood
  • Melatonin / metabolism*
  • Photoperiod
  • Pyridines / pharmacology*
  • Sleep
  • Wakefulness
  • Zolpidem


  • Hypnotics and Sedatives
  • Pyridines
  • Zolpidem
  • Melatonin