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Melatonin Does Not Shift Circadian Phase in Baboons¹

Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Dr. Scott A. Rivkees, Department of Pediatrics, Yale University School of Medicine, 464 Congress Avenue, YCHRC, Room 239, New Haven, Connecticut 06520. E-mail: scott.rivkees{at}yale.edu

It has been suggested that the pineal hormone melatonin can modulate circadian rhythmicity and may have clinical utility in treating biological clock disorders. Thus, there is considerable clinical interest in using melatonin to treat disorders, such as jet-lag. Yet, despite growing enthusiasm for the use of melatonin, it is not clear whether melatonin indeed shifts the circadian phase in humans and other primate species. Thus, to assess whether melatonin can influence circadian phase, we studied the phase-shifting effects of melatonin on baboons to provide insights into the role of melatonin. Melatonin was administered orally to baboons (0.5, 3, 5, or 10 mg) either in the early morning hours from circadian time (CT) 0 to CT3 or late in the afternoon from CT9 to CT12, and changes in circadian phase were assessed. Surprisingly, at all doses and times tested, melatonin did not shift circadian phase. Physical activity was reduced after 5- and 10-mg doses given late in the afternoon, but not after doses given early in the morning. These observations suggest that melatonin does not shift circadian phase in baboons using doses similar to those prescribed for treating human circadian system disorders.

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