• Sack, Robert (PI)

Project: Research project

Project Details


Melatonin is a hormone produced by the pineal gland at night that may be
involved in the natural regulation of circadian rhythms. Animal studies
have shown that exogenous melatonin administration can synchronize "free-
running" circadian rhythms and can accelerate the rate of adaptation to a
new rest/activity cycle. In studies currently in progress, we administered
melatonin orally to five totally blind subjects with free-running
endogenous melatonin rhythms in an attempt to entrain them to a 24-hour
day. Although entrainment did not result, melatonin treatment produced
large phase advances in the endogenous melatonin rhythms. These advances
are much more robust than when melatonin is given to sighted people,
possibly because the competing time cues from the light-dark cycle are not
present in the blind subjects. In this project, we will evaluate the constraining effects of the light-
dark cycle by giving melatonin to both blind and sighted subjects. We will
define the parameters that produce the maximal phase-advancing effects in
both groups by varying the timing, dose and duration of melatonin
administration. We will attempt to enhance the phase-advancing effects of
exogenous melatonin administration by suppressing endogenous melatonin
production with the drug atenolol will test the effects of melatonin in
sighted subjects who are adapting to an abrupt advance of their sleep-wake
cycle (a laboratory model of shift work adaptation). We will evaluate the phase-advancing effects of exogenous melatonin
administration by measuring its effect on the timing (phase) of endogenous
melatonin production by the pineal gland. Phase will be assessed by
obtaining serial blood samples and measuring plasma melatonin
concentrations to determine the precise "onset" of active production. An
RIA will be employed for efficiently processing most of the samples but
critical values around the time of the melatonin onset will be verified
with a highly specific gas chromatographic negative ion mass spectrometric
assay. These studies may lead to the use of melatonin as a way to treat
both blind and sighted patients with abnormal circadian rhythms.
Effective start/end date3/1/912/28/95


  • National Institutes of Health


  • Medicine(all)


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