Effect of melatonin on sleep and brain temperature in the Djungarian hamster and the rat (original) (raw)
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Chronic administration of melatonin reduces REM sleep in the Djungarian hamster (Phodopus sungorus)
Neuroscience Letters, 1997
The prominent effects of photoperiod on sleep, electroencephalogram power spectra and cortical temperature in the Djungarian hamster may be mediated by melatonin. We investigated the effects of chronic subcutaneous melatonin application on these variables in Djungarian hamsters recorded in a short photoperiod (light/dark 8:16 h). Melatonin abolished the light/dark difference in vigilance state distribution, reduced the amount of rapid eye movement (REM) sleep in the light period and the occurrence of REM sleep episodes. In contrast to the reduction of both cortical temperature and electroencephalogram power density in hamsters adapted to a short photoperiod these variables were unaffected by melatonin. Since the effects of chronic application of melatonin differ from those of shortening of the photoperiod it is improbable that melatonin mediates the effects.
The Role of Melatonin in Human Thermoregulation and Sleep
Early studies and research work on the physiological effects of melatonin typically reported hypnotic 'side-effects'. Later studies, specifically addressing and focusing this action, failed to reliably replicate hypnotic effects using standard polysomnography. This difference may be rakished to differences in the basic physiological action of melatonin to induce sleep compared with more conventional hypnotics.
Sleep, 1997
Differing conclusions regarding the sleep-promoting effects of melatonin may be the result of the broad range of doses employed (0.1-2000 mg), the differing categories of subjects tested (normal subjects, insomniac patients, elderly, etc.), and the varying times of administration (for daytime vs. nighttime sleep). We conclude that melatonin may benefit sleep by correcting circadian phase abnormalities and/or by a modest direct soporific effect that is most evident following daytime administration to younger subjects. We speculate that these effects are mediated by interactions with specific receptors concentrated in the suprachiasmatic nucleus (SCN) that result in resetting of the circadian pacemaker and/or attenuation of an SCN-dependent circadian alerting process.
Efficacy of Melatonin as a Sleep-Promoting Agent
Journal of Biological Rhythms, 1997
Numerous studies have demonstrated sleep-promoting effects of melatonin treatment in humans, as evidenced by subjects' self-reports, polysomnographic recordings, and continuous actigraphic registration of motor activity. The sleep-promoting effects of either physiological or pharmacological doses of melatonin typically are observed within 1 h following treatment regardless of the time of melatonin administration. This fact indicates the acute nature of this effect of melatonin on sleep, independent of any effect of the melatonin treatment on circadian organization. This article considers a dose dependency of melatonin effects on sleep, interindividual variability, and age-related differences in circulating melatonin levels produced in response to a given dose of the hormone. Possible side effects of melatonin treatment, and the use of an animal model to serve as a guide in the development of therapeutic applications, also are considered.
Sleep-inducing effects of exogenous melatonin administration
Sleep Medicine Reviews, 1998
In this report current data is reviewed indicating that melatonin, the main hormone secreted by the pineal gland at night, participates in sleep regulation in humans. Evidence supporting this role relies on findings that abnormal melatonin secretion, induced by a variety of commonly used drugs, and in clinical disorders of the nervous system, are associated with sleep disturbances, and that melatonin has beneficial sleep-inducing efiects in elderly melatonin-deficient insomniacs, and in children with sleep disorders. The time of melatonin administration, rather than the pharmacological dose, is a crucial factor regarding its potency as a sleep-inducing agent. Possible operating mechanisms explaining melatonin hypnotic effects are discussed.
2010
The thermoregulatory system is tied to the regulation of sleep and wakefulness. Research protocols have examined the unmasked effect of endogenous melatonin on these systems by giving exogenous doses under controlled conditions during the daytime, when endogenous levels are low. Study findings have demonstrated that exogenous melatonin improves sleep, increases peripheral heat loss, and decreases core body temperature (CBT). These thermoregulatory adjustments mimic those that occur around habitual bedtime, when endogenous melatonin levels are high. The emergences of artificial light and stimulants i.e., caffeine have impacted the behavior and physiology that normally precede sleep. Caffeine may independently impact sleep/wakefulness, or in conjunction with the thermoregulatory system. Bright light during the biological night suppresses melatonin and changes the thermoregulatory pattern that precedes nocturnal sleep; these changes may ultimately impact the sleep/wakefulness system. To improve our understanding of physiological mechanisms promoting and disrupting sleep/wakefulness, it is important to examine the connection between melatonin and the sleep/wakefulness and thermoregulatory systems, and the impact of environmental and behavioral factors on these systems. Therefore, the aims of this dissertation were to: 1) determine the effect of a melatonin receptor analogue ramelteon, on daytime sleep and body temperature, and the relationship between the two variables; 2) determine the effect of daytime exogenous melatonin on resting iv energy expenditure, (REE); and 3) determine the individual and compound effects of caffeine and bright light on thermoregulatory and sleep physiology at night. Consistent with our hypotheses, 1) ramelteon significantly improved daytime sleep, lowered CBT, and increased peripheral heat loss 2) exogenous melatonin decreased REE during the daytime, and 3) caffeine delayed the nocturnal rise in peripheral heat loss, attenuated the fall in CBT, while the combination of caffeine and bright light decreased slow wave sleep and increased sleep onset latency. These findings suggest that melatonin may play an important role in the regulation of sleep/wakefulness as evidenced by the effect of daytime ramelteon administration on sleep and thermoregulatory physiology and the effect of daytime exogenous melatonin on REE. Finally, caffeine and bright light had a negative impact on nocturnal sleep and these effects may be mediated in part by their impact on the thermoregulatory system.
Thermoregulatory effects of melatonin in relation to sleepiness
Chronobiology International, 2006
Thermoregulatory processes have long been implicated in the initiation of human sleep. In this paper, we review our own studies conducted over the last decade showing a crucial role for melatonin as a mediator between the thermoregulatory and arousal system in humans. Distal heat loss, via increased skin temperature, seems to be intimately coupled with increased sleepiness and sleep induction. Exogenous melatonin administration during the day when melatonin is essentially absent mimics the endogenous thermophysiological processes occurring in the evening and induces sleepiness. Using a cold thermic challenge test, it was shown that melatonininduced sleepiness occurs in parallel with reduction in the thermoregulatory set-point (threshold); thus, melatonin may act as a circadian modulator of the thermoregulatory set-point. In addition, an orthostatic challenge can partially block the melatonin-induced effects, suggesting an important role of the sympathetic nervous system as a link between the thermoregulatory and arousal systems. A topographical analysis of finger skin temperature with infrared thermometry revealed that the most distal parts of the fingers, i.e., fingertips, represent the important skin regions for heat loss regulation, most probably via opening the arteriovenous anastomoses, and this is clearly potentiated by melatonin. Taken together, melatonin is involved in the fine-tuning of vascular tone in selective vascular beds, as circulating melatonin levels rise and fall throughout the night. Besides the role of melatonin as "nature's soporific", it can also serve as nature's nocturnal vascular modulator.
Proceedings of the National Academy of Sciences, 1994
We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin dos...
Role of Melatonin in the Regulation of Human Circadian Rhythms and Sleep
Journal of Neuroendocrinology, 2003
The circadian rhythm of pineal melatonin is the best marker of internal time under low ambient light levels. The endogenous melatonin rhythm exhibits a close association with the endogenous circadian component of the sleep propensity rhythm. This has led to the idea that melatonin is an internal sleep 'facilitator' in humans, and therefore useful in the treatment of insomnia and the readjustment of circadian rhythms. There is evidence that administration of melatonin is able: (i) to induce sleep when the homeostatic drive to sleep is insufficient; (ii) to inhibit the drive for wakefulness emanating from the circadian pacemaker; and (iii) induce phase shifts in the circadian clock such that the circadian phase of increased sleep propensity occurs at a new, desired time. Therefore, exogenous melatonin can act as soporific agent, a chronohypnotic, and/or a chronobiotic. We describe the role of melatonin in the regulation of sleep, and the use of exogenous melatonin to treat sleep or circadian rhythm disorders.