Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night (original) (raw)
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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.
The effects of day-time exogenous melatonin administration on cardiac autonomic activity
Journal of Pineal Research, 2001
Melatonin has a functional role in the nocturnal regulation of sleep and thermoregulation. In addition to its action on peripheral receptors, melatonin may act by altering autonomic activity. To determine the effect of melatonin on cardiac autonomic activity, 5 mg of melatonin or placebo was orally administered to 12 young subjects at 14:00 hr, in a repeated measures design. Melatonin decreased sleep onset latency to Stage 2 sleep by 4.929 1.81 min (measured by Multiple Sleep Latency Tests), rectal temperature by 0.199 0.05°C, and increased foot temperature by 0.749 0.45°C (all PB 0.05). Melatonin decreased heart rate by 3.6691.68 beats/min (P B0.05) and pre-ejection period (measure of cardiac sympathetic activity) by 16.48 9 4.28 ms (P B0.05), but had no effect on respiratory sinus arrhythmia (measure of cardiac parasympathetic activity) (P\ 0.05). As the decrease in pre-ejection period is likely to have resulted from a decrease in blood pressure, these results do not confirm an effect of melatonin on cardiac sympathetic activity. However, the results do clearly indicate that melatonin is unlikely to drive the previously observed presleep increase in cardiac parasympathetic activity.
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.
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...
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.
Neuroscience Letters, 1997
This constant routine study (n = 9 men) compared the phase delay of the circadian system induced by a single pulse of evening light (5000 lx at 2100-2400 h) in the presence or absence of exogenous melatonin (5 mg p.o. at 2040 h). On the treatment day, light and melatonin protracted and accelerated, respectively, the evening decline in core body temperature (CBT). Subjective sleepiness ratings showed parallel shifts, the earlier the decline in CBT, the sleepier. On the post-treatment day, light induced a phase delay in the mid-range crossing time of CBT decline independent of whether melatonin was co-administered or not. Subjective sleepiness was delayed in parallel. The phase delay of the circadian system by evening light appears to be independent of an immediate hyperthermic effect and is not mediated by melatonin.
Day-time melatonin administration: Effects on core temperature and sleep onset latency
Journal of Sleep Research, 1996
Significant hypothermic and hypnotic effects have been reported for melatonin at a wide range of doses. It has been suggested that this decrease in core temperature (Tc) following melatonin administration may mediate the observed increase in sleepiness. To test this, melatonin was administered to young adults during the day, and the concurrent effects on Tc and sleep onset latency (SOL) were recorded. Sixteen healthy males received either a 5 mg oral formulation of melatonin or placebo at 14.00 hours. Core temperature was recorded continuously. Sleep onset latency to stage 1 (SOL1) and stage 2 (SOL2) were recorded using an hourly multiple sleep latency test (MSLT). Compared with placebo, melatonin significantly decreased Tc 1.5 h after administration for 6 h. Between 15.00 and 18.00 hours, the drop in Tc was associated with a concurrent decrease in SOL1 and SOL2. Following administration mean SOL1 and SOL2 were reduced by 40 and 25%, respectively. In this study, daytime melatonin administration produced a significant decrease in Tc with a corresponding decrease in SOL. Taken together, these data are not inconsistent with the suggestion that melatonin may facilitate sleep onset via a hypothermic effect. In addition, this study provides support for the idea that melatonin may play a role in regulating circadian and/or age-related variations in sleep/wake propensity. From a practical perspective, exogenous melatonin may be useful in the treatment of sleep disorders associated with increased nocturnal Tc.
Effect of melatonin on sleep and brain temperature in the Djungarian hamster and the rat
Physiology & Behavior, 1998
Effect of melatonin on sleep and brain temperature in the Djungarian hamster and rat. PHYSIOL BEHAV 65(1) [77][78][79][80][81] 1998.-The effect of a single dose of melatonin (3-5 mg/kg intraperitoneally) on sleep, electroencephalographic power density, and cortical temperature (T CRT ) was investigated. Melatonin was administered to Djungarian hamsters 4 h or 12 h after lights on in a 16-h light:8-h dark cycle (LD 16:8) and to rats at dark onset in a LD 12:12. The effects in both species were short lasting and depended on the time of day. Sleep latency was prolonged in the late light period, sleep fragmentation was enhanced in the early light period, and T CRT was elevated in all three conditions. Rapid eye-movement sleep was reduced in the first postdrug hour after the late light period treatment in the hamsters and in postdrug hours 2 and 3 after dark onset treatment in the rat. Therefore, we have no evidence for a sleep inducing effect of 3-5 mg/kg of melatonin in the hamster or rat. In view of some data that indicate that melatonin may exert a sleep inducing effect in humans, it is suggested that melatonin induces changes that are typical for the dark period of each species, i.e., waking in the nocturnal Djungarian hamster and rat, and sleepiness in the diurnal human.
Complex effects of melatonin on human circadian rhythms in constant dim light
Journal of biological rhythms, 1997
In humans, the pineal hormone melatonin can phase shift a number of circadian rhythms (e.g., "fatigue," endogenous melatonin, core body temperature) together with the timing of prolactin secretion. It is uncertain, however, whether melatonin can fully entrain all human circadian rhythms. In this study, the authors investigated the effects of daily melatonin administration on sighted individuals kept in continuous very dim light. A total of 10 normal, healthy males were maintained in two separate groups in partial temporal isolation under constant dim light (< 8 lux) with attenuated sound and ambient temperature variations but with knowledge of clock time for two periods of 30 days. In these circumstances, the majority of individuals free run with a mean period of 24.3 h. In a double-blind, randomized crossover design, subjects received 5 mg melatonin at 20:00 h on Days 1 to 15 (Melatonin 1st) followed by placebo on Days 16 to 30 (Placebo 2nd) or vice versa (Placebo 1st, Melatonin 2nd) during Leg 1 with treatment reversed in Leg 2. The variables measured were melatonin (as 6sulphatoxymelatonin), rectal temperature, activity, and sleep (actigraphy and logs). In the experiment, 9 of the 10 subjects free ran with Placebo 1st, whereas Melatonin 1st stabilized the sleep-wake cycle to 24 h in 8 of 10 individuals. In addition, 2 individuals showed irregular sleep with this treatment. In some subjects, there was a shortening of the period of the temperature rhythm without synchronization. Melatonin 2nd induced phase advances (5 of 9 subjects), phase delays (2 of 9 subjects), and stabilization (2 of 9 subjects) of the sleep-wake cycle with subsequent synchronization to 24 h in the majority of individuals (7 of 9). Temperature continued to free run in 4 subjects. Maximum phase advances in core temperature were seen when the first melatonin treatment was given approximately 2 h after the temperature acrophase. These results indicate that melatonin was able to phase shift sleep and core temperature but was unable to synchronize core temperature consistently. In the majority of subjects, the sleepwake cycle could be synchronized.
Sleep, 1997
Melatonin has been shown to have hypnotic and hypothermic effects in young adults and has been proposed as treatment for insomnia. However, the hypnotic and thermoregulatory effects of melatonin remain to be simultaneously investigated for aged good and poor sleepers. The aim of this study was to explore the shortterm effects of exogenous oral daytime melatonin on core body temperature, sleep latency, and subjective vigor and affect in aged women. Twelve sleep maintenance insomniacs and 10 good ~Ieeping postmenopausal female subjects [mean (SD) age = 65.2 (7.4) years] participated in a double-blind, crossover study in which they received a capsule containing either melatonin (5 mg) or a placebo at 1400 hours. Continuous core body temperature and hourly mUltiple sleep latency tests (MSLT) were collected from 1100-2030 hours. Self-reported estimates of global vigor (sleepiness) and affect were collected prior to each MSLT using visual analog scales. Comparison of good and poor sleepers failed to reveal any significant differences in core body temperature, sleep latency, or subjective vigor and affect. However, for both groups combined, melatonin administration [absolute postadministration mean (SEM) = 36.9 (0.05tC] significantly lowered core body temperature compared with placebo [37.1 (0.05tC]. Similarly, melatonin administration significantly reduced latency to stage I (SOLI) and stage 2 (SOL2) [absolute postadministration mean SOLI = 20.1 (1.7) and SOL2 = 20.7 (1.6) minutes] compared with placebo [SOLI = 24.3 (1.2) and SOL2 = 25.2 (1.1) minutes]. Treatment had no significant effect on either vigor or affect. Overall, our results suggest that although short-term exogenous oral daytime melatonin has significant hypothermic and hypnotic effects in aged women, the size of the effects is modest.