Pineal and retinal melatonin is involved in the control of circadian locomotor activity and body temperature rhythms in the pigeon

Summary Although pinealectomy or blinding resulted in loss of the clarity of the free-running rhythm of locomotor activity and body temperature and reduced the peak level of circulating melatonin rhythms to approximately a half in intact pigeons, neither pinealectomy nor blinding abolished any of these rhythms. However, when pinealectomy and blinding were combined, the rhythms of locomotor activity and body temperature disappeared in prolonged constant dim light, and melatonin concentration was reduced to the minimum level of detection. In order to examine the role of melatonin in the pigeon's circadian system, it was administered either daily or continuously to PX + EX-pigeons in LLdim. Daily administration of melatonin restored circadian rhythms of locomotor activity which entrained to melatonin injections, but continuous administration did not induce any remarkable change of locomotor activity. These results suggest that melatonin synthesized in the pineal body and the eye contributes to circulating melatonin and its rhythmicity is important for the control of circadian rhythms of locomotor activity and body temperature in the pigeon.Abbreviations LD Light-dark - LLdim constant dim light - LLbright constant bright light - PX pinealectomy - EX blinding - SCN suprachiasmatic nucleus     

Association of the melatonin circadian rhythms with clock 3111T/C gene polymorphism in Caucasian and Asian menopausal women with insomnia

A comparative analysis of melatonin circadian rhythms in Caucasian (incoming population) and Asian (indigenous population) menopausal women with/without sleep disorders depending on the genotype of Clock 3111T/C gene polymorphism was realized.The melatonin level in the saliva was determined four times a day (6:00–7:00, 12:00–13:00, 18:00–19:00, 23:00–00:00 h). The Caucasian women—carriers of the TT-genotype with insomnia as compared to control group—had a higher morning melatonin level and a lower night melatonin level. The Asian women with TT-genotype and insomnia had a lower levels of melatonin as compared to control at daytime, evening and night. A significantly higher melatonin level in the early morning hours was detected in the Caucasian women—carriers of the TT-genotype with insomnia as compared to group womencarriers of the minor 3111C-allele. There were no statistically significant differences in the circadian rhythms of melatonin in the Asian women depending on the genotype of the Clock 3111T/C polymorphism. An assumption with respect to the protective role of the minor allele 3111C in the development of insomnia associated with the displacement of melatonin circadian rhythms in the representatives of the incoming population was made.     

β-carotene ameliorates CUS-induced circadian alternations of locomotor activity and melatonin patterns in rats

Circadian and stress systems have a crucial role in adaptation of organisms to environmental challenges. This study investigates the ability of Oscillatoria brevis (O. brevis) β-carotene extract (βC) in modulating the circadian alternations of locomotor activity (LA) and serum melatonin (M) rhythms under chronic unpredictable stress (CUS) in rats. Twenty rats (5 rats/group) were used in monitoring LA using running wheels. Eighty rats (20 rats/group) were used in observing circadian serum M profile. Rats were randomly divided into four groups, viz. control, βC-treated, CUS-exposed, and “βC-treated&CUS-exposed” groups. CUS-exposure was applied for 21 days. One hour before exposure, βC was daily administered (10 mg/kg), intraperitoneally (IP). Blood was sampled at 6-h intervals for 5 rats/time point at Zeitgeber (ZT) 3, 9, 15, and 21. Results demonstrated that unstressed rats exhibited circadian M pattern and nocturnal LA rhythm with acrophase around ZT 21 and ZT 15, respectively. CUS-exposure revealed a disturbance in these patterns. Phase shifting of M and LA profiles was recorded. A decrease M acrophase and a significant decrease in LA (p < 0.05) were recorded at ZT 9. Daily βC administration in stressed rats modulates the CRs alternation induced by CUS. It may be concluded that βC ameliorated the induced alternations in circadian rhythms.     

Feeding rhythms in constant light and constant darkness: the role of the eyes and the effect of melatonin infusion

Exposure to constant light abolishes circadian behavioral rhythms of locomotion and feeding as well as circulating melatonin rhythms in pigeons (Columba livia). To determine if feeding rhythmicity could be maintained in pigeons exposed to constant light, periodic infusions (10h/day) of melatonin were administered to pinealectomized and bilaterally retinectomized/pinealectomized pigeons under conditions of both constant darkness and constant light. The infusions were sufficient to entrain rhythmicity in pinealectomized pigeons in constant darkness and to restore and maintain rhythmicity in bilaterally retinectomized/pinealectomized pigeons in constant darkness. On subsequent exposure to constant light, rhythmicity remained phase locked to the melatonin infusions in bilaterally retinectomized/pinealectomized pigeons but was abolished in sighted pinealectomized birds. These results suggest that while endogenous melatonin rhythms are both necessary and sufficient to maintain behavioral rhythms in DD, their effect can be overridden by constant light but only if perceived by the eyes. Thus, constant light may abolish behavioral rhythmicity in intact pigeons (and perhaps in other species) by a mechanism other than suppression of endogenous melatonin rhythmicity. Such a mechanism might involve direct stimulation of locomotor or feeding activity by retinally perceived (but not by extra-retinally perceived) light, or alternatively by suppression of a hypothalamic oscillator that receives its major light input from the retinae.Abbreviations PX pinealectomized - EX bilaterally enucleated - LD light:dark cycle - LL constant light - DD constant darkness - DD_b constant darkness before exposure to constant light - DD_a constant darkness after exposure to constant light     

Effects of radiation emanating from base transceiver station and mobile phone on sleep,circadian rhythm and cognition in humans – a review

The electromagnetic fields (EMF) are ubiquitous. The base transceiver station (BTS) and mobile phones (MPs) contribute to the generation of EMF around their locations and are regarded as important sources of non-ionizing radiations. The use of mobile phone has increased dramatically in recent years so also the skepticism regarding its effects. In this review, we have made an attempt to scan the key research papers those aimed at elucidating the effects of EMF starting from extreme low frequency (ELF) to radio frequency (RF) through low frequency (LF). We have selected papers that dealt with the effects of radiations emanating from the BTS and MPs on human sleep, circadian rhythm, and cognition. Mostly, we have concentrated on papers published in the last 15 years. We came across conflicting reports. The findings reported in many papers suggest that the exposure to EMF has potentiality to compromise parameters related to sleep quality; in contrast, there are several reports those have given a clean sheet to the EMF exposure. The effects of EMF on circadian rhythms also remain inconclusive. The EMF exposure while did not produce any effect on circadian rhythm of heart rate and blood chemistry, it modulated the rhythms in cortisol and melatonin characterized by a decline in their 24-h circulating levels. The effects of exposure to EMF on cognitive parameters, like performance and memory, are also equivocal. The existing contradictory findings could be attributed to inter-individual variability in tolerance, gender-, and age-dependent differences in response, latitudinal differences in efficacy, variability among employed methodologies and differences in specific absorption rate, frequency of the mobile phone usage, and interaction of EMF with other physiological and environmental factors, among others. The future research should be carried out with added focus on elucidating the modulatory effects of these factors to put an end to the existing controversies on the biological effects of low/RF EMF radiations.     

Restricted daytime feeding attenuates reentrainment of the circadian melatonin rhythm after an 8-h phase advance of the light-dark cycle

It is well established that in the absence of photic cues, the circadian rhythms of rodents can be readily phase-shifted and entrained by various nonphotic stimuli that induce increased levels of locomotor activity (i.e., benzodiazepines, a new running wheel, and limited food access). In the presence of an entraining light-dark (LD) cycle, however, the entraining effects of nonphotic stimuli on (parts of) the circadian oscillator are far less clear. Yet, an interesting finding is that appropriately timed exercise after a phase shift can accelerate the entrainment of circadian rhythms to the new LD cycle in both rodents and humans. The present study investigated whether restricted daytime feeding (RF) (1) induces a phase shift of the melatonin rhythm under entrained LD conditions and (2) accelerates resynchronization of circadian rhythms after an 8-h phase advance. Animals were adapted to RF with 2-h food access at the projected time of the new dark onset. Before and at several time points after the 8-h phase advance, nocturnal melatonin profiles were measured in RF animals and animals on ad libitum feeding (AL). In LD-entrained conditions, RF did not cause any significant changes in the nocturnal melatonin profile as compared to AL. Unexpectedly, after the 8-h phase advance, RF animals resynchronized more slowly to the new LD cycle than AL animals. These results indicate that prior entrainment to a nonphotic stimulus such as RF may "phase lock" the circadian oscillator and in that way hinder resynchronization after a phase shift.     

Circadian rhythms of melatonin in haemolymph and optic lobes of Chinese mitten crab (Eriocheir sinensis) and Chinese grass shrimp (Palaemonetes sinensis)

This study is the first to examine the circadian rhythms of melatonin in Eriocheir sinensis and Palaemonetes sinensis, two economically important crustaceans. We collected haemolymph and optic lobes from both species every 4 h over a whole day cycle. Melatonin content was measured with high-performance liquid chromatography. E. sinensis haemolymph exhibited significant (p < 0.05) peaks in melatonin at 16:00 (0.180 ± 0.020 μg·mL^?1) and 24:00 (0.244 ± 0.055 μg·mL^?1), while eyestalks had significant peaks at 16:00 (72.377 ± 18.100 μg·eyestalk^?1) and 24:00 (98.756 ± 30.271 μg·eyestalk^?1). In P. sinensis, melatonin peaked significantly only at 16:00 in optic lobes (12.493 ± 1.475 μg·eyestalk^?1) (p < 0.05); no significant peaks were present in haemolymph. Thus, both E. sinensis and P. sinensis exhibit species-specific melatonin rhythms. Time of day should therefore be considered when examining the physiological status of both crustaceans, given the potential influence of fluctuating daily melatonin concentrations.     

Circadian rhythm gene expression and daily melatonin levels vary in athletes and sedentary males

The circadian rhythm is a 24-h cycle in which cells control metabolic and physiological processes throughout the day. In this study, we compared the expression patterns of major circadian rhythm-related genes: from blood of Bmal1, Ror-α, Cry1, Per2, Per1, and Nr1d1. In addition, changes in patterns of melatonin levels were observed in 16 subjects, eight males rugby players and eight males who did not exercise regularly. Blood was collected at 6:00, 10:00, 18:00, and 22:00. Bmal1, Ror-α, Cry1, Per2 (p < 0.001), Per1 (p < 0.01), and Nr1d1 (p < 0.05) genes related to circadian rhythm was higher in rugby players than in sedentary males. However, melatonin levels were higher in sedentary males than in rugby players (p < 0.05). These results indicate that long-term exercise in athletes can increase the expression of genes related to circadian rhythm and these may have an effect on daily melatonin levels as well.     

Loss of the circadian rhythms of locomotor activity, food intake, and plasma melatonin concentration induced by constant bright light in the pigeon (Columba livia)

Summary Locomotor activity and feeding activity were measured together with circulating levels of melatonin in pigeons which were exposed to constant bright light (LLbright, 2000 lux) following light-dark (LD) cycles. Although all the pigeons showed daily rhythms of locomotor activity, feeding activity, and melatonin levels under LD cycles, they lost all the rhythms in prolonged LLbright. Acute exposure to bright light (2000 lux) during darkness reduced plasma melatonin levels. The half-time for the suppression in melatonin levels was about 30 min after short-term light exposure. These results support the hypothesis that melatonin may control the circadian rhythms of locomotor activity and feeding activity in the pigeon.Abbreviations LD light-dark - LLdim constant dim light - LLbright constant bright light - DD constant darkness - PX pinealectomy - EX blinding - RIA radioimmunoassay     

Circadian organization in the pigeon,Columba livia: the role of the pineal organ and the eye

Summary The roles of the pineal organ and the eye in the control of circadian locomotor rhythmicity were studied in the pigeon (Columba livia). Neither pinealectomy nor blinding abolished the circadian rhythms in constant dim light conditions (LLdim). All the pinealectomized birds and the blinded birds entrained to light-dark (LD) cycles with no discernible anticipatory activity. However, the birds which had been both pinealectomized and blinded showed no circadian rhythms in prolonged LLdim. These birds entrained to LD cycles with anticipatory activity and showed residual rhythmicity for a while after transfer from LD cycles to LLdim. Continuous administration of melatonin induced suppression of the circadian rhythms and reduced total amount of locomotor activity in LLdim. These results suggest that not only the pineal organ but also the eye (perhaps the retina) is involved in the pigeon's circadian system.Abbreviations NAT N-acetyltransferase - LLdim constant dim light - cadian period - SCN suprachiasmatic nucleus - circadian activity time - LD light-dark     

Comparing the response to acute and chronic exposure to short wavelength lighting emitted from computer screens

The use of electronic devices with light-emitting screens has increased exponentially in the last decade. As a result, humans are continuously exposed to unintentional artificial light. We explored the effects of acute and chronic exposure to artificial light at night (ALAN) via screen illumination on sleep, circadian rhythms, and related functional outcomes. Nineteen participants (11 female and 8 males, mean age 28.1 ± 7.2 years) underwent a six-night study with three experimental conditions using a repeated-measures design: baseline (first night, no light exposure), acute ALAN exposure (second night), and chronic ALAN exposure (third to sixth nights). Each light exposure lasted for 2 hours (21:00–23:00). Participants underwent an overnight polysomnography at the end of each condition (nights 1, 2, and 6). We collected urine samples (for melatonin metabolite analysis), while body (oral) temperatures were measured before and after exposure. Each morning, the participants filled out questionnaires and conducted a computerized attention test. Both acute and chronic illumination significantly disrupted sleep continuity and architecture and led to greater self-reported daytime sleepiness, negative emotions, and attention difficulties. Both exposure types also altered circadian rhythms, subduing the normal nocturnal decline in body temperature and dampening nocturnal melatonin secretion. In sum, ALAN exposure from electronic screens has an immediate, detrimental, yet stable effect on sleep, circadian regulation, and next-day functional outcomes. Given the widespread use of electronic devices today, our findings suggest that even one night of screen light exposure may be sufficient to cause adverse effects on health and performance.     

Effects of obstructive sleep apnea on endogenous circadian rhythms assessed during relaxed wakefulness; an exploratory analysis

ABSTRACT

Obstructive sleep apnea (OSA) is associated with hypertension, cardiovascular disease, and a change in the 24 h pattern of adverse cardiovascular events and mortality. Adverse cardiovascular events occur more frequently in the middle of the night in people with OSA, earlier than the morning prevalence of these events in the general population. It is unknown if these changes are associated with a change in the underlying circadian rhythms, independent of behaviors such as sleep, physical activity, and meal intake. In this exploratory analysis, we studied the endogenous circadian rhythms of blood pressure, heart rate, melatonin and cortisol in 11 participants (48 ± 4 years; seven with OSA) throughout a 5 day study that was originally designed to examine circadian characteristics of obstructive apnea events. After a baseline night, participants completed 10 recurring 5 h 20 min behavioral cycles divided evenly into standardized sleep and wake periods. Blood pressure and heart rate were recorded in a relaxed semirecumbent posture 15 minutes after each scheduled wake time. Salivary melatonin and cortisol concentrations were measured at 1–1.5 h intervals during wakefulness. Mixed-model cosinor analyses were performed to determine the rhythmicity of all variables with respect to external time and separately to circadian phases (aligned to the dim light melatonin onset, DLMO). The circadian rhythm of blood pressure peaked much later in OSA compared to control participants (group × circadian phase, p < .05); there was also a trend toward a slightly delayed cortisol rhythm in the OSA group. Rhythms of heart rate and melatonin did not differ between the groups. In this exploratory analysis, OSA appears to be associated with a phase change (relative to DLMO) in the endogenous circadian rhythm of blood pressure during relaxed wakefulness, independent of common daily behaviors.     

Bright-light exposure during daytime sleeping affects nocturnal melatonin secretion after simulated night work

The guidelines for night and shift workers recommend that after night work, they should sleep in a dark environment during the daytime. However, staying in a dark environment during the daytime reduces nocturnal melatonin secretion and delays its onset. Daytime bright-light exposure after night work is important for melatonin synthesis the subsequent night and for maintaining the circadian rhythms. However, it is not clear whether daytime sleeping after night work should be in a dim- or a bright-light environment for maintaining melatonin secretion. The aim of this study, therefore, was to evaluate the effect of bright-light exposure during daytime sleeping on nocturnal melatonin secretion after simulated night work. Twelve healthy male subjects, aged 24.8 ± 4.6 (mean ± SD), participated in 3-day sessions under two experimental conditions, bright light or dim light, in a random order. On the first day, the subjects entered the experimental room at 16:00 and saliva samples were collected every hour between 18:00 and 00:00 under dim-light conditions. Between 00:00 and 08:00, they participated in tasks that simulated night work. At 10:00 the next morning, they slept for 6 hours under either a bright-light condition (>3000 lx) or a dim-light condition (<50 lx). In the evening, saliva samples were collected as on the first day. The saliva samples were analyzed for melatonin concentration. Activity and sleep times were recorded by a wrist device worn throughout the experiment. In the statistical analysis, the time courses of melatonin concentration were compared between the two conditions by three-way repeated measurements ANOVA (light condition, day and time of day). The change in dim light melatonin onset (ΔDLMO) between the first and second days, and daytime and nocturnal sleep parameters after the simulated night work were compared between the light conditions using paired t-tests. The ANOVA results indicated a significant interaction (light condition and3 day) (p = .006). Post hoc tests indicated that in the dim-light condition, the melatonin concentration was significantly lower on the second day than on the first day (p = .046); however, in the bright-light condition, there was no significant difference in the melatonin concentration between the days (p = .560). There was a significant difference in ΔDLMO between the conditions (p = .015): DLMO after sleeping was advanced by 11.1 ± 17.4 min under bright-light conditions but delayed for 7.2 ± 13.6 min after sleeping under dim-light conditions. No significant differences were found in any sleep parameter. Our study demonstrated that daytime sleeping under bright-light conditions after night work could not reduce late evening melatonin secretion until midnight or delay the phase of melatonin secretion without decreasing the quality of the daytime sleeping. Thus, these results suggested that, to enhance melatonin secretion and to maintain their conventional sleep–wake cycle, after night work, shift workers should sleep during the daytime under bright-light conditions rather than dim-light conditions.     

Melatonin-induced phase and dose responses in a diurnal mammal,Funambulus pennantii

ABSTRACT

Melatonin, an essential pineal hormone, acts as a marker of the circadian clock that regulates biological rhythms in animals. The effects of exogenous melatonin on the circadian system of nocturnal rodents have been extensively studied; however, there is a paucity of studies on the phase-resetting characteristics of melatonin in diurnal rodents. We studied the phase shifting effects of exogenous melatonin as a single melatonin injection (1 mg/kg) at various phases of the circadian cycle on the circadian locomotor activity rhythm in the palm squirrel, Funambulus pennantii. A phase response curve (PRC) was constructed. Adult male squirrels (N = 10) were entrained to a 12:12 h light-dark cycle (LD) in a climate-controlled chronocubicle with food and water provided ad libitum. After stable entrainment, squirrels were transferred to constant dark condition (DD) for free-running. Following stable free run, animals were administered a single dose of melatonin (1 mg/kg in 2% ethanol-phosphate buffered saline (PBS) solution) or vehicle (2% ethanol-PBS solution) at circadian times (CTs) 3 h apart to evoke phase shifts. The phase shifts elicited at various CTs were plotted to generate the PRC. A dose response curve was generated using four doses (0.5, 1, 2 and 4 mg/kg) administered at the CT of maximum phase advance. Melatonin evoked maximum phase advances at CT0 (1.23 ± 0.28 h) and maximum phase delays at CT15 (0.31 ± 0.09 h). In the dose response experiment, maximal phase shifts were evoked with 1 mg/kg. In contrast, no significant shifts were observed in control groups. Our study demonstrates that the precise timing and appropriate dose of melatonin administration is essential to maximize the amelioration of circadian rhythm–related disorders in a diurnal model.     

The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes

Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100?mg?day^?1 of melatonin or placebo 30?min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00?h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep–wake cycle, improving sleep efficiency.     

Melatonin Accelerates Reentrainment After Phase Advance of the Light-dark Cycle in Syrian Hamsters: Antagonism by Flumazenil

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D -2, D -1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, ∼ 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.     

Hypothermia after chronic mild stress exposure in rats with a history of postnatal maternal separations

The circadian system develops and changes in a gradual and programmed process over the lifespan. Early in life, maternal care represents an important zeitgeber and thus contributes to the development of circadian rhythmicity. Exposure to early life stress may affect circadian processes and induce a latent circadian disturbance evident after exposure to later life stress. Disturbance of the normal regulation of circadian rhythmicity is surmised to be an etiological factor in depression. We used postnatal maternal separation in rats to investigate how the early life environment might modify the circadian response to later life unpredictable and chronic stress. During postnatal days 2–14, male Wistar rats (n?=?8 per group) were daily separated from their mothers for a period of either 180?min (long maternal separation; LMS) or 10?min (brief maternal separation; BMS). In adulthood, rats were exposed to chronic mild stress (CMS) for 4 weeks. Body temperature, locomotor activity and heart rate were measured and compared before and after CMS exposure. LMS offspring showed a delayed body temperature acrophase compared to BMS offspring. Otherwise, adult LMS and BMS offspring demonstrated similar diurnal rhythms of body temperature, locomotor activity and heart rate. Exposure to CMS provoked a stronger and longer lasting hypothermia in LMS rats than in BMS rats. The thermoregulatory response appears to be moderated by maternal care following reunion, an observation made in the LMS group only. The results show that early life stress (LMS) in an early developmental stage induced a thermoregulatory disturbance evident upon exposure to unpredictable adult life stressors.     

Melatonin Accelerates Reentrainment After Phase Advance of the Light-dark Cycle in Syrian Hamsters: Antagonism by Flumazenil

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D -2, D -1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, ～ 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.     

Melatonin suppression during a simulated night shift in medium intensity light is increased by 10-minute breaks in dim light and decreased by 10-minute breaks in bright light

ABSTRACT

Exposure to light at night results in disruption of endogenous circadian rhythmicity and/or suppression of pineal melatonin, which can consequently lead to acute or chronic adverse health problems. In the present study, we investigated whether exposure to very dim light or very bright light for a short duration influences melatonin suppression, subjective sleepiness, and performance during exposure to constant moderately bright light. Twenty-four healthy male university students were divided into two experimental groups: Half of them (mean age: 20.0 ± 0.9 years) participated in an experiment for short-duration (10 min) light conditions of medium intensity light (430 lx, medium breaks) vs. very dim light (< 1 lx, dim breaks) and the other half (mean age: 21.3 ± 2.5 years) participated in an experiment for short-duration light conditions of medium intensity light (430 lx, medium breaks) vs. very bright light (4700 lx, bright breaks). Each simulated night shift consisting of 5 sets (each including 50-minute night work and 10-minute break) was performed from 01:00 to 06:00 h. The subjects were exposed to medium intensity light (550 lx) during the night work. Each 10-minute break was conducted every hour from 02:00 to 06:00 h. Salivary melatonin concentrations were measured, subjective sleepiness was assessed, the psychomotor vigilance task was performed at hourly intervals from 21:00 h until the end of the experiment. Compared to melatonin suppression between 04:00 and 06:00 h in the condition of medium breaks, the condition of dim breaks significantly promoted melatonin suppression and the condition of bright breaks significantly diminished melatonin suppression. However, there was no remarkable effect of either dim breaks or bright breaks on subjective sleepiness and performance of the psychomotor vigilance task. Our findings suggest that periodic exposure to light for short durations during exposure to a constant light environment affects the sensitivity of pineal melatonin to constant light depending on the difference between light intensities in the two light conditions (i.e., short light exposure vs. constant light exposure). Also, our findings indicate that exposure to light of various intensities at night could be a factor influencing the light-induced melatonin suppression in real night work settings.     

Effects of constant darkness and constant light on circadian organization and reproductive responses in the ram

The relationship between circadian rhythms in the blood plasma concentrations of melatonin and rhythms in locomotor activity was studied in adult male sheep (Soay rams) exposed to 16-week periods of short days (8 hr of light and 16 hr of darkness; LD 8:16) or long days (LD 16:8) followed by 16-week periods of constant darkness (dim red light; DD) or constant light (LL). Under both LD 8:16 and LD 16:8, there was a clearly defined 24-hr rhythm in plasma concentrations of melatonin, with high levels throughout the dark phase. Periodogram analysis revealed a 24-hr rhythm in locomotor activity under LD 8:16 and LD 16:8. The main bouts of activity occurred during the light phase. A change from LD 8:16 to LD 16:8 resulted in a decrease in the duration of elevated melatonin secretion (melatonin peak) and an increase in the duration of activity corresponding to the changes in the ratio of light to darkness. In all rams, a significant circadian rhythm of activity persisted over the first 2 weeks following transfer from an entraining photoperiod to DD, with a mean period of 23.77 hr. However, the activity rhythms subsequently became disorganized, as did the 24-hr melatonin rhythms. The introduction of a 1-hr light pulse every 24 hr (LD 1:23) for 2 weeks after 8 weeks under DD reinduced a rhythm in both melatonin secretion and activity: the end of the 1-hr light period acted as the dusk signal, producing a normal temporal association of the two rhythms. Under LL, the 24-hr melatonin rhythms were disrupted, though several rams still showed periods of elevated melatonin secretion. Significant activity rhythms were either absent or a weak component occurred with a period of 24 hr. The introduction of a 1-hr dark period every 24 hr for 2 weeks after 8 weeks under LL (LD 23:1) failed to induce or entrain rhythms in either of the parameters. The occurrence of 24-hr activity rhythm in some rams under LL may indicate nonphotoperiodic entrainment signals in our experimental facility. Reproductive responses to the changes in photoperiod were also monitored. After pretreatment with LD 8:16, the rams were sexually active; exposure to LD 16:8, DD, or LL resulted in a decline in all measures of reproductive function. The decline was slower under DD than LD 16:8 or LL.(ABSTRACT TRUNCATED AT 400 WORDS)