Phase shifting the human circadian clock using melatonin
Behavioural Brain ResearchPublished 1 December 1995
Alfred J. Lewy, Saeeduddin Ahmed, Robert L. Sack
Citations94
SJR quartileQ2
SJR score0.92
SNIP0.77
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
A phase response curve (PRC) to melatonin in humans that is about 12 h out of phase with the PRC to light is described, which may function to augment entrainment of circadian rhythms by the light-dark cycle.
Abstract
Melatonin is produced only during nighttime darkness. Its onset during the evening is a useful marker for circadian phase position, when melatonin levels are sampled frequently and under conditions of dim light or darkness. This marker is termed the dim light melatonin onset (DLMO). Recently, we have described a phase response curve (PRC) to melatonin in humans that is about 12 h out of phase with the PRC to light. Exogenous melatonin administration and bright light exposure can be used to shift circadian rhythms according to their respective PRCs. These phase-resetting agents can be used alone or together to treat circadian phase disorders, which include advanced and delayed sleep phase syndrome, shift work maladaptation, jet lag and winter depression. Endogenous melatonin may function to augment entrainment of circadian rhythms by the light-dark cycle.
Keywords
Neuroscience
Brain ResearchLoss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat
2,108 Citations1972Robert Y. Moore, Victor B. Eichler
The purpose of the present study was to reinvestigate the role of the central retinal projections in neuroendocrine regulation and find that lesions in the suprachiasmatic region of the hypothalamus abolish the constant estrous response to light in the female rat.
Proceedings of the National Academy of SciencesCircadian Rhythms in Drinking Behavior and Locomotor Activity of Rats Are Eliminated by Hypothalamic Lesions
2,015 Citations1972Friedrich K. Stephan, Irving H. Zucker
Bilateral electrolytic lesions in the suprachiasmatic nuclei permanently eliminated nocturnal and circadian rhythms in drinking behavior and locomotor activity of albino rats.
ScienceLight Suppresses Melatonin Secretion in Humans
1,913 Citations1980Alfred J. Lewy, Thomas A. Wehr +3 more
Findings establish that the human response to light is qualitatively similar to that of other mammals.
ScienceIndole Metabolism in the Pineal Gland: A Circadian Rhythm in <i>N</i> -Acetyltransferase
746 Citations1970David C. Klein, Joan L. Weller
Experiments in vitro indicate that norepinephrine, not serotonin, regulates the activity of N-acetyl-transferase through a highly specific receptor.
ScienceAntidepressant and Circadian Phase-Shifting Effects of Light
714 Citations1987Alfred J. Lewy, Robert L. Sack +2 more
The antidepressant response to morning light was accompanied by an advance in the onset of nighttime melatonin production, suggesting that timing may be critical for the antidepressant effects of bright light.
Chronobiology InternationalMelatonin Shifts Human Orcadian Rhythms According to a Phase-Response Curve
697 Citations1992Alfred J. Lewy, Saeeduddin Ahmed +2 more
The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel.
Neuroscience LettersA human phase-response curve to light
638 Citations1991David Minors, James Waterhouse +1 more
The human phase-response curve (PRC) to a single 3-h bright light pulse does not differ in principle from that found in other species, except with respect to the light intensity required.
SciencePutative Melatonin Receptors in a Human Biological Clock
505 Citations1988Steven M. Reppert, David R. Weaver +2 more
The results suggest that putative melatonin receptors are located in a human biological clock, and specifically found in the suprachiasmatic nuclei of hypothalami from adults and fetuses.
ScienceEnzymatic O-Methylation of N-Acetylserotonin to Melatonin
438 Citations1960Julius Axelrod, Herbert Weissbach
An enzyme, hydroxyindole-O-methyl transferase, that can transfer the methyl group of S-adenosylmethionine to the hydroxy group of N-acetylserotonin to form the hormone melatonin is described.
Chronobiology InternationalThe Dim Light Melatonin Onset as a Marker for Orcadian Phase Position
417 Citations1989Alfred J. Lewy, Robert L. Sack
By measuring the onset of melatonin production, a clearly demarcated event, the authors can reliably assess circadian phase position, provided blood is sampled under dim light (the dim light melatonin onset, or DLMO), which has been useful in assessing the phase-shifting properties of bright light and in phase typing patients with chronobiologic disorders, such as winter depression.
Archives of General PsychiatryMorning vs Evening Light Treatment for Winter Depression
180 Citations1990Robert L. Sack
It is suggested that patients with winter depression have circadian rhythms that are abnormally delayed and that bright light therapy benefits winter depression by providing a corrective advance.
NeuroendocrinologyMelatonin Is Able to Influence Its Secretion in Humans: Description of a Phase-Response Curve
171 Citations2008Radwan Zaidan, M. Geoffriau +5 more
Results, which show that according to a PRC the system regulating melatonin secretion is sensitive to a single short-term administration of the hormone given at a low dose, support the paradigm of the endogenous synchronizer melatonin.
Journal of Comparative Physiology ACircadian phase response curves for dark pulses in the hamster
161 Citations1982Ziad Boulos, Benjamin Rusak
Hamsters maintained under constant illumination were exposed to 2- or 6-h pulses of darkness at various phases of their circadian activity rhythms, indicating that phase response curves for light and dark pulses are mirror images.
Novartis Foundation symposiumSome Effects of Melatonin and the Control of its Secretion in Humans
130 Citations1985Joséphine Arendt, C. Bojkowski +8 more
The results suggest that fatigue (or alertness) may be entrained by melatonin, but whether critical performance rhythms can be suitably manipulated remains to be clarified.
Behavioural Brain ResearchMelatonin receptors in the mammalian suprachiasmatic nucleus
86 Citations1995Margarita L. Dubocovich, Susan Benloucif +1 more
Evidence is presented suggesting that activation of melatonin receptors in the SCN regulates circadian rhythms of behavior in the mouse, suggesting that melatonin may be important in synchronizing circadian rhythms to changes in the natural photoperiod.
European Journal of EndocrinologyEffects of a four-day nocturnal melatonin treatment on the 24 h plasma melatonin, cortisol and prolactin profiles in humans
56 Citations1988C Mallo, Radwan Zaidan +4 more
It is suggested that melatonin, when administered at a high dose over a short period, can influence the endocrine rhythms, and especially its own endogenous secretion.
Journal of Pineal ResearchCircadian Rhythms in Lizards: Phase Response Curve for Melatonin
53 Citations1986Herbert Underwood
The existence of a phase‐response curve (PRC) for melatonin suggests that the daily endogenous rhythm of melatonin may be involved in phasing, or entraining, the circadian system of lizards.