• Sack, Robert (PI)

Project: Research project

Project Details


The is an application for an ADAMHA Research Scientist Award (Level II).
The candidate will use the award to devote his full professional energies
to research projects at the interface of psychiatry, sleep disorders
medicine and circadian rhythms. He will focus particularly on the
development of melatonin as a treatment for disorders of circadian phase. 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 this project, the constraining effects of the light-dark cycle will be
evaluated by giving melatonin to both blind and sighted subjects. The
parameters that produce the maximal phase-advancing effects in both groups
will be defined by varying the timing, dose and duration of melatonin
administration. An attempt to enhance the phase-advancing effects of
exogenous melatonin will be made by the co-administration of melatonin with
atenolol, a drug that suppresses endogenous melatonin production by
blocking pineal beta adrenergic receptors. After defining the optimal
treatment parameters, 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) will be tested. The phase-advancing effects of exogenous melatonin administration will be
evaluated 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.
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 date4/1/923/31/98


  • National Institutes of Health


  • Medicine(all)


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