Relationship between light intensity and the melatonin and drinking rhythms of rats

We examined the effect of varying ambient light intensity on the amplitudes of the daily rhythms in urinary melatonin excreted or water consumed per day. Animals were initially exposed to one of two types of diurnal regimens (dim light: darkness or bright light: darkness) designed to simulate their lighting situations in nature or in the laboratory. They were then placed under continuous light, at one of four intensities: total darkness, very dim light (0.005-0.01 microW/cm2), dim light (0.1-0.3 microW/cm2) and bright light (45-110 microW/cm2). Under continuous lighting the amplitudes of melatonin rhythms and the concentrations of melatonin excreted per 24-hour period decreased as the intensity of illumination was increased. A 50% decrease in the rhythm's amplitude, compared with the amplitude observed when the same rats had been under a diurnal lighting regimen, required irradiances of about 0.05 microW/cm2, which is on the same order as the intensity provided by full moonlight (0.20 microW/cm2). Water consumption rhythms were less altered by continuous light: only the brightest irradiances (45-110 microW/cm2) significantly reduced amplitude by 40-60%.     

Suppression of Melatonin Secretion in Île-de-France Rams by Different Light Intensities

The intensity of cool, white, fluorescent light required to suppress melatonin secretion in Ile-de-France rams was investigated. Animals were conditioned to 12L:12D, lights on 0600 hours, 104 microW/cm2 (350 lux) at eye level and subjected to a 1-hour light pulse beginning 3 hours after lights off. Plasma melatonin measurements indicated that secretion was significantly suppressed by 0.30, 7.46, and 26.32 microW/cm2 (1.02, 25.10, and 88.60 lux, respectively) but not by 0.043 microW/cm2 (0.15 lux). A clear dose-response relationship was apparent between light intensity and degree of melatonin suppression.     

Adaptation of human pineal melatonin suppression by recent photic history

The human circadian pacemaker controls the timing of the release of the pineal hormone melatonin, which promotes sleep, decreases body temperature, and diminishes cognitive performance. Abnormal melatonin secretion has been observed in psychiatric and circadian disorders. Although melatonin secretion is directly suppressed by exposure to light in a nonlinear intensity-dependent fashion, little research has focused on the effect of prior photic history on this response. We examined eight subjects in controlled laboratory conditions using a within-subjects design. Baseline melatonin secretion was monitored under constant routine conditions and compared with two additional constant routines with a fixed light stimulus for 6.5 h of 200 lux (50 microW/cm(2)) after approximately 3 d of photic exposure during the subjective day of either about 200 lux (50 microW/cm(2)) or about 0.5 lux (0.15 microW/cm(2)). We found a significant increase in melatonin suppression during the stimulus after a prior photic history of approximately 0.5 lux compared with approximately 200 lux, revealing that humans exhibit adaptation of circadian photoreception. Such adaptation indicates that translation of a photic stimulus into drive on the human circadian pacemaker involves more complex temporal dynamics than previously recognized. Further elucidation of these properties could prove useful in potentiating light therapies for circadian and affective disorders.     

Diurnal Changes in Serum Melatonin Concentrations Under Indoor and Outdoor Environments and Light Suppression of Nighttime Melatonin Secretion in the Female Japanese Monkey

To examine whether artificial light with the intensity commonly used for animal experimentation can mimic natural sunlight with respect to diurnal changes in serum melatonin, and to determine the minimum light intensity required to suppress nocturnal melatonin, serum melatonin profiles were examined in groups of female Japanese monkeys (Macaca fuscata fuscata). Under outdoor environment, light intensities at the level of the monkey's eyes varied during daytime (0900-1500 h) depending on weather conditions (minimum and maximum on particular experimental days: 170 lux at 0900 h on a rainy day and 9500 lux at 0900 h on a slightly cloudy day); under indoor environment, light was provided by ordinary fluorescent bulbs that resulted in intensities of 400-500 lux at the level of monkey's eyes. No difference was found in diurnal changes in serum melatonin concentrations regardless of weather or housing conditions: Serum melatonin remained low during daytime and increased during nighttime. Following exposure to light, irradiances of 10,000, 400-500, 100-140, 50-100, and 10-30 lux at midnight resulted in a rapid decrease in serum melatonin to daytime levels within 1 to 2 h. After the onset of dark, serum melatonin reverted to previous nighttime levels within 2 h. Exposure to a light irradiance of 2-5 lux, however, did not suppress nocturnal melatonin secretion. It is concluded that artificial light can mimic natural sunlight with respect to melatonin secretion in the female Japanese monkey, and that light of 10-30 lux irradiance was sufficient to suppress serum melatonin to near daytime levels.     

Prolonged suppression of serum concentrations of melatonin in prepubertal heifers

Our objective was to suppress the daily surge of melatonin in serum of prepubertal dairy heifers by manipulating intensity of light (Experiment 1) and duration of exposure to light (Experiment 2). Heifers in Experiment 1 were exposed to either 12 hr of darkness (000 lux, control), or 400, 800, or 1,200 lux of light during the last 6 hr of their usual 12-hr nocturnal period. During this 6-hr exposure to various intensities of light, melatonin concentrations were similar to their respective daytime baseline values measured under 400 lux of light, but were 62% to 82% lower than melatonin concentrations during their nocturnal surge period. Suppression of melatonin concentrations was similar between 400 and 1,200 lux of light. In Experiment 2, heifers were exposed to LD 8:16, LD 16:8, LD 20:4, or LD 24:0 photoperiods (1,200 lux) for 4 months. Throughout treatment, concentrations and durations of the melatonin surge were suppressed in the LD 24:0 group and were greatest (during the nocturnal period) in the LD 8:16 group. Concentrations of prolactin in serum were elevated in animals under long days relative to LD 8:16 treatment and respective pretreatment periods. In conclusion, continuous light at an intensity of 1,200 lux suppressed the nocturnal surge of melatonin, but increased secretion of prolactin for at least 4 months in prepubertal heifers.     

The Influence of Various Irradiances of Artificial Light, Twilight, and Moonlight on the Suppression of Pineal Melatonin Content in the Syrian Hamster

The purpose of the present studies using artificial light was to determine how the timing and duration of exposure influence the light-induced suppression of pineal melatonin levels in hamsters. An 8-min exposure to 0.186 microW/cm2 of cool white fluorescent light caused a continued depression of pineal melatonin even when animals were returned to darkness. In addition, the pineal gland does not appear to change its sensitivity to light throughout the night. A 20-min exposure to 0.019 microW/cm2 of cool white fluorescent light did not significantly suppress pineal melatonin during any time of the melatonin peak, whereas a 20-min exposure to 0.186 microW/cm2 was capable of always suppressing melatonin. Furthermore, increasing the duration of 0.019-microW/cm2 exposure to 30, 60, 120, or 180 min does not increase the capacity of this irradiance to depress melatonin. Similar to artifical light, natural light has a variable capacity for suppressing nocturnal levels of pineal melatonin. Twilight irradiances of 0.138 microW/cm2 or less did not suppress nocturnal melatonin whereas twilight irradiances of 3.0 microW/cm2 or greater did suppress pineal melatonin. A few animals did have lower melatonin after a 40-min exposure to full moonlight during July (0.045 microW/cm2) or January (0.240 microW/cm2). However, pineal melatonin levels remained high in the majority of animals exposed to full moonlight.     

The suppression of nocturnal pineal melatonin in the Syrian hamster: dose-response curves at 500 and 360 nm

It has recently been shown that wavelengths in the near-UV range (UV-A, 320-400 nm) are capable of influencing pineal melatonin content in the hamster. The purpose of this study was to compare the capacities of monochromatic visible and UV radiation for suppressing nocturnal pineal melatonin. Groups of male Syrian hamsters adapted to a 14-h light, 10-h dark cycle (lights on, 1700-0700 h) were exposed to irradiances of 500 or 360 nm light for 5 min during their dark phase. Both wavelengths suppressed pineal melatonin in a dose-related manner. The resultant fluence-response curves were similar in shape, although their corresponding threshold irradiances were markedly different. The calculated ED50 values for 500 and 360 nm light were 0.022 microW/cm2 (1.66 X 10(13) photons/cm2) and 0.306 microW/cm2 (1.66 X 10(14) photons/cm2), respectively. These data show that the induction of a 50% depression of pineal melatonin requires 10 times the number of 360-nm photons compared to 500-nm photons at the level of the cornea. Despite this difference in sensitivity to wavelength, environmental irradiances of UV-A are well above the threshold for melatonin suppression in the hamster. These results thus demonstrate the importance of considering UV-A, in addition to the visible wavelengths, in the regulation of hamster pineal physiology.     

Human Melatonin Suppression by Light is Intensity Dependent

Five intensities of artificial light were examined for the effect on nocturnal melatonin concentrations. Maximum suppression of melatonin following 1 hr of light at midnight was 71%, 67%, 44%, 38%, and 16% with intensities of 3,000, 1,000, 500, 350, and 200 lux (lx), respectively. In contrast to some previous reports, light of 1,000 lx intensity was sufficient to suppress melatonin to near daytime levels, and intensities down to 350 lx were shown to significantly suppress nocturnal melatonin levels below prelight values. On the basis of these data, it is suggested that when examining the melatonin sensitivity of patient groups (such as bipolar affective disorders) to artificial light, an appropriate light intensity should be established in each laboratory. Light of less intensity (e.g., 200-350 lx) may be more suitable to dichotomize patient groups from control subjects.     

Phase Delay of the Rhythm of 6-Sulphatoxy Melatonin Excretion by Artificial Light

The purpose of this study was to investigate the effect of bright artificial light exposure on the rhythms of 6-sulphatoxy melatonin cortisol excretion in urine. Six healthy males were exposed to light (> 3,000 lux) from 1900 to 0200 h (sunset 1928 h) on one occasion. The artificial light delayed the onset of 6-sulphatoxy melatonin excretion. On the next evening the onset of 6-sulphatoxy melatonin excretion in normal light/darkness was delayed by 1 h. The timing of the peak excretion of cortisol was not affected by the light treatment; however, cortisol excretion rate was maintained at a signficantly higher rate in the morning afternoon after the treatment. These results demonstrate the inhibitory action of high intensity light in humans suggest that one 6-h period of extra light in the evening can phase delay the melatonin onset.     

Non-suppressibility by room light of pineal N-acetyltransferase activity and melatonin levels in two diurnally active rodents, the Mexican ground squirrel (Spermophilus mexicanus) and the eastern chipmunk (Tamias striatus)

The rhythms in pineal N-acetyltransferase (NAT) activity and melatonin levels were studied in the diurnally active Mexican ground squirrel and Eastern chipmunk. In the ground squirrel, both NAT activity and melatonin levels exhibited a marked nocturnal rise; these increases were not prevented by the exposure of these animals to a light irradiance of 200 microW/cm2 throughout the night. In the Eastern chipmunk, darkness at night was also associated with a marked rise in both the activity of the acetylating enzyme as well as the levels of melatonin. Again, these rhythms were not suppressed by the exposure of these animals to a light irradiance of 200 microW/cm2 for either 1 night or for 7 nights; exposure of chipmunks to light for 7 consecutive days did, however, reduce the rise in melatonin normally associated with darkness. The non-suppressibility of pineal NAT and melatonin by a 200 microW/cm2 light irradiance may relate either to the activity pattern of these animals, i.e., diurnal, or to their previous lighting history.     

Photoreceptor damage and eye pigmentation: influence on the sensitivity of rat pineal N-acetyltransferase activity and melatonin levels to light at night

The threshold of light irradiance capable of inhibiting nighttime pineal serotonin N-acetyltransferase (NAT) activity and melatonin content, and the importance of intact photoreceptors and eye pigmentation on these changes, were investigated in the rat. Groups of intact albino and black-eyed rats and albino animals with light-induced photoreceptor damage were studied in the dark period before, and after 15 and 30 min of exposure to either 0.0005, 0.175 or 3.33 microW/cm2 irradiance of light. In animals with photoreceptor damage, the sensitivity of the pineal gland to light decreased so that only the highest irradiance tested (3.33 microW/cm2) was capable of totally inhibiting pineal NAT activity and melatonin levels. In one study, pineal NAT and melatonin levels in intact albino rats were inhibited by all three irradiances studied. In a second experiment, albino and black-eyed animals behaved identically, only responding with a depression in pineal NAT and melatonin after exposure to light irradiances of either 0.175 or 3.33 microW/cm2. In conclusion, the lowest irradiance of cool white light capable of inhibiting pineal NAT and melatonin in albino rats is around 0.0005 microW/cm2. At the irradiances studied, photoreceptor damage influences the response of pineal NAT and melatonin to acute light exposure at night. On the other hand, eye pigmentation does not seem to have a major effect on the nighttime inhibition of the pineal by light.     

Blue blocker glasses impede the capacity of bright light to suppress melatonin production

Blocking morning light exposure with dark goggles can contribute to the adjustment to night work but these glasses are incompatible with driving. Recently, it was discovered that the biological clock is most sensitive to short wavelengths (blue light). Therefore, we tested the hypothesis that cutting the blue portion of the light spectrum with orange lens glasses (blue blockers) would prevent the light-induced melatonin suppression, a test broadly used as an indirect assessment of the circadian clock sensitivity. Fourteen normal subjects were exposed at night to a 60 min bright light pulse (1300 lx behind filters) between 01:00 and 02:00 hr while wearing orange lens glasses (experimental condition) or grey lens glasses (control condition). The amount of salivary melatonin change observed during the light pulse was compared with a melatonin baseline obtained the night before. Although both glasses transmitted the same illuminance (1300 lx) but at an irradiance 25% higher for the orange lens (408 microW/cm2) compared with the grey lens (327 microW/cm2), a non-significant increase of 6% (95% CI, -20% to 9%) was observed with the orange lens whereas a significant (P < 0.05) reduction of 46% (95% CI, 35-57%) was observed with the grey lens. Blue blockers represent an elegant means to prevent the light-induced melatonin suppression. Further studies are needed to show that these glasses, which are suitable for driving, could facilitate adaptation to night work.     

Light Suppression of Melatonin in the Squirrel Monkey (Saimiri sciureus)

This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12:12 light-dark cycle (LD 12:12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionization mass spectrometry. Melatonin levels at 00:00 (99.5 +/- 18.9 pg/ml) were significantly higher than at 02:00 (57.21 +/- 7.7 pg/ml; Student's t = 2.859; P less than or equal to 0.021). Baseline values at 02:00 were compared with levels at the same time of day after exposure to 2 hours of 200 lux of light (30.6 +/- 13.1 pg/ml), which caused an average suppression of 54.8% in melatonin levels. One animal did not show light suppression. Results indicated that the squirrel monkey suppressant response to light, as well as baseline values of melatonin, varied between animals.     

Responsiveness of Pineal N-Acetyltransferase and Melatonin in the Cotton Rat Exposed to Either Artificial or Natural Light at Night

In three separate experiments, the effect of acute exposure to either artificial or natural light during darkness of pineal N-acetyltransferase (NAT) activity and melatonin content was studied in the cotton rat (Sigmodon hispidus). The exposure of animals to an artificial-light irradiance of 160,000 microW/cm2 during darkness for either 1 s, 5 s, or 30 min was followed by a precipitous decline in pineal NAT activity and melatonin content when measured at either 15 or 30 min after light onset. When cotton rats were acutely exposed to light at night for 5 s, irradiances of either 3.2, 32, 320, and 3,200 did not suppress either pineal NAT or melatonin 30 min later; however, if the 5-s exposure had an irradiance of either 32,000 or 160,000 microW/cm2, the pineal enzyme activity and indole content were depressed. Moonlight, which had a maximal irradiance of 0.32 microW/cm2, was unable to suppress pineal NAT activity and melatonin content even when the animals were exposed to the moonlight for 30 min. The treatment of cotton rats with either norepinephrine or its agonist, isoproterenol, before their exposure to light at night retarded slightly the suppressive effect of light on the pineal constituents measured. Also, these drug treatments suppressed the pre-exposure levels of both NAT activity and melatonin content in the cotton rat pineal gland.     

Blocking low-wavelength light prevents nocturnal melatonin suppression with no adverse effect on performance during simulated shift work

Decreases in melatonin production in human and animals are known to be caused by environmental lighting, especially short-wavelength lighting (between 470 and 525 nm). We investigated the novel hypothesis that the use of goggles with selective exclusion of all wavelengths less than 530 nm could prevent the suppression of melatonin in bright-light conditions during a simulated shift-work experiment. Salivary melatonin levels were measured under dim (<5 lux), bright (800 lux), and filtered (800 lux) light at hourly intervals between 2000 and 0800 h in 11 healthy young males and eight females (mean age, 24.7 +/- 4.6 yr). The measurements were performed during three nonconsecutive nights over a 2-wk period. Subjective sleepiness was measured by self-report scales, whereas objective performance was assessed with the Continuous Performance Test. All subjects demonstrated preserved melatonin levels in filtered light similar to their dim-light secretion profile. Unfiltered bright light drastically suppressed melatonin production. Normalization of endogenous melatonin production while wearing goggles did not impair measures of performance, subjective sleepiness, or alertness.     

A single 1- or 5-second light pulse at night inhibits hamster pineal melatonin

Adult male Syrian hamsters maintained under 6-h light, 18-h dark cycles (lights out daily from 1200-0600 h) were exposed to either 1 or 5 sec light either 8 h (at 2000 h) or 12 h (at 2400 h) into the dark phase. The light had an irradiance of 32,000 microW/cm2. With both light pulse durations and at both times, melatonin levels were depressed to daytime values 30 min after the onset of the light pulse. Whereas pineal melatonin production eventually increased to high nighttime values in hamsters exposed to 1 sec light at either 2000 or 2400 h and in animals receiving a 5-sec light pulse at 2000 h, when the 5-sec light occurred at 2400 h, pineal melatonin levels remained low for the remainder of the night. Thus, both the placement and the duration of light exposure appear to be important in determining the ability of light to depress melatonin production in the Syrian hamster.     

The effects of light exposure on plasma concentrations of melatonin, LH, FSH and prolactin in women

The effects of light exposure on plasma concentrations of melatonin, LH, FSH and prolactin were studied in 11 normal cycling women during their follicular phases. Blood samples were obtained via an indwelling venous catheter every 10 min. for 2.5 hours starting at 9:30 and 21:30h. For the blood samplings taken at night, six women were kept in a dark room and were permitted to sleep. Their blood samples were obtained using a flashlight (5-10 lux) without their rest being disturbed. However, the other five women were exposed to light (3,000 lux at eye level) and awakened from 22:40 to 24:00h. Plasma melatonin concentrations in the morning decreased from 48.7 +/- 11.6 pg/ml at 9:30h to 24.7 +/- 4.0 pg/ml at 12:00h. On the other hand, plasma melatonin concentrations at night increased from 65.4 +/- 9.6 pg/ml at 21:30h to 138.2 +/- 28.6 pg/ml at 24:00h. The pulsatile LH secretion was changed from the type of "high frequency, low amplitude" in the morning to the type of "low frequency, high amplitude" at night. Nocturnal FSH concentrations were lower than diurnal ones, but nocturnal prolactin concentrations were higher than diurnal ones. Nocturnal concentrations of melatonin were suppressed 40 min. after the light exposure (from 117.4 +/- 11.4 pg/ml at 22:40h to 74.6 +/- 13.9 pg/ml at 23:20h). On the the other hand, the light exposure increased plasma prolactin concentrations from 10.9 +/- 4.1 ng/ml at 22:40h to 17.0 +/- 4.4 ng/ml at 22:50h, maintained those higher levels for 20 min. and decreased them gradually after 23:20h. With the light exposure, mean values of nocturnal LH concentrations were increased from 11.9 +/- 1.5 mIU/ml before exposure to 14.2 +/- 1.8 mIU/ml after exposure, and those of FSH were also increased from 5.9 +/- 0.4 mIU/ml to 6.3 +/- 0.4 mIU/ml. These results showed that the secretion of melatonin, as well as LH, FSH and prolactin had daily rhythms and that melatonin and prolactin showed different responses to light exposure, suggesting different control mechanisms for the secretion of those two hormones.     

Influence of light intensity, spectrum and orientation on sea bass plasma and ocular melatonin

Melatonin is involved in the transduction of light information and the photoperiodic control of many important physiological functions in fish. Although artificial photoperiods have been used to improve fish growth and manipulate reproduction, there is little information about the characteristics of light 'quality'. In this paper we describe the effects of a light pulse in the middle of the dark phase on plasma and ocular melatonin in European sea bass. We first determined the light intensity necessary to elicit a melatonin response using white light of varying intensities (0.6-600 mu W/cm(2), experiment 1). Secondly, we tested the effect of the light spectrum on melatonin production using three differently coloured lights (half-peak bandwidth=434-477, 498-575 and 610-687 nm for the blue, green and red lamp, respectively, experiment 2) and, finally, we determined the effect of light orientation (downwards directed versus upwards directed, experiment 3). The results show that the minimum light intensity needed to inhibit or stimulate melatonin levels in both plasma and the eye was 6.0 mu W/cm(2). A linear correlation was found between the logarithm of light intensity and the relative inhibition. In addition, the blue wavelength was more effective in decreasing melatonin levels in the former and increasing the levels in the latter. Nevertheless, red light at sufficient intensity proved effective at significantly suppressing circulating melatonin. Downwards light had a greater effect than upward-directed illumination in suppressing plasma melatonin. In conclusion, the results point to the importance of giving proper consideration to the characteristics of light, to adequately control melatonin production and its related physiological processes.     

Effects of a two-hour early awakening and of bright light exposure on plasma patterns of cortisol, melatonin, prolactin and testosterone in man.

Bright light is a synchronizing agent that entrains human circadian rhythms and modifies various endocrine and neuroendocrine functions. The aim of the present study was to determine whether and how the exposure to a bright light stimulus during the 2 h following a 2 h earlier awakening could modify the disturbance induced by the the sleep deprivation on the plasma patterns of hormones whose secretion is sensitive to light and/or sleep, namely melatonin, prolactin, cortisol and testosterone. Six healthy and synchronized (lights on: 07.00-23.00) male students (22.5 +/- 1.1 years) with normal psychological profiles volunteered for the study in winter. The protocol consisted of a baseline control night (customary sleep schedule) followed by three shortened nights with a rising at 05.00 and a 2 h exposure to either dim light (50 lux; one week) or bright light (2000 lux; other week). Our study showed a phase advance of the circadian rhythm of plasma cortisol without significant modifications of the hormone mean or peak concentration. Plasma melatonin concentration decreased following bright light exposure, whereas no obvious modifications of plasma testosterone or prolactin patterns could be observed in this protocol.     

Effects of melatonin on the thermoregulatory responses to intermittent exercise

We examined the effects of a single 2.5-mg dose of melatonin on the thermoregulatory and circulatory responses to intermittent exercise at a room temperature of 27.2+/-0.4 degrees C (mean+/-S.D.), a relative humidity of 55+/-3% (mean+/-S.D.), and a light intensity of 200-300 lux. In a double-blind cross-over study, six male participants ingested either melatonin or placebo at 11:45 hr. Participants then rested in a semi-supine position for 75 min and completed an intermittent running protocol for 66 min at alternating intensities of 40, 60 and 80% of maximal oxygen uptake. Rectal and mean skin temperature, heart rate, blood pressure, skin blood flow, subjective alertness and sleepiness, ratings of perceived exertion (RPE) and thermal strain were recorded. No effects of melatonin were found on these variables measured during the resting period (P>0.10). During exercise, melatonin was found to moderate the increase in rectal temperature by approximately 0.25 degrees C (P=0.050) and magnify the increase in skin blood flow (P=0.047). Postexercise systolic blood pressure was 7.8+/-2.5 mmHg (mean+/-S.D.) lower than before the exercise in the melatonin trial; a change which differed significantly to that in the placebo trial (P=0.018). Melatonin did not influence subjective alertness and sleepiness before or after exercise and did not change the responses of mean skin temperature, RPE and thermal strain during the exercise (P>0.10). In summary it is apparent that a 2.5-mg dose of melatonin has hypothermic, but not soporific, effects during 66 min of intermittent exercise performed under moderate heat stress. Whether such effects improve endurance athletic performance in hot conditions remains to be confirmed. Our data also suggest that postexercise systolic hypotension is more marked after ingestion of melatonin.