Bright artificial light subsensitizes a central muscarinic mechanism

Supersensitivity of a muscarinic mechanism is implicated in the pathophysiology of depression. Bright artificial light is efficacious in the treatment of Seasonal Affective Disorder (SAD). We studied the effect of constant bright light (11,500 lux) on the sensitivity of adult, male rats to oxotremorine, 1.5 mg/kg ip, using a repeated measures design. Oxotremorine challenges were proceeded by the injection of methylscopolamine, 1 mg/kg ip, by 30 minutes. Temperature was telemetrically measured every 10 minutes for 120 minutes starting 10 minutes after the injection of oxotremorine. Prior to and after 7 continuous days of exposure to bright light, the sample exhibited a hypothermic response of 2.50 +/- 0.48 degrees C (mean +/- SEM) and 0.29 +/- 0.31 degrees C (mean +/- SEM), respectively (p less than 0.0014). All 7 animals exhibited blunting to the thermic response to oxotremorine. Bright light also blocked the capacity of amitriptyline to supersensitize a central muscarinic mechanism. Exposure to light at an intensity of 300 lux for 7 days had no effect on the thermic response to oxotremorine. These data are consistent with the hypotheses that the biology of depression involves supersensitivity of central muscarinic mechanisms and that the effects of bright artificial light are not the consequence of shifting circadian rhythms.     

Efficacy of a single sequence of intermittent bright light pulses for delaying circadian phase in humans

It has been shown in animal studies that exposure to brief pulses of bright light can phase shift the circadian pacemaker and that the resetting action of light is most efficient during the first minutes of light exposure. In humans, multiple consecutive days of exposure to brief bright light pulses have been shown to phase shift the circadian pacemaker. The aim of the present study was to determine whether a single sequence of brief bright light pulses administered during the early biological night would phase delay the human circadian pacemaker. Twenty-one healthy young subjects underwent a 6.5-h light exposure session in one of three randomly assigned conditions: 1) continuous bright light of approximately 9,500 lux, 2) intermittent bright light (six 15-min bright light pulses of approximately 9,500 lux separated by 60 min of very dim light of <1 lux), and 3) continuous very dim light of <1 lux. Twenty subjects were included in the analysis. Core body temperature (CBT) and melatonin were used as phase markers of the circadian pacemaker. Phase delays of CBT and melatonin rhythms in response to intermittent bright light pulses were comparable to those measured after continuous bright light exposure, even though the total exposure to the intermittent bright light represented only 23% of the 6.5-h continuous exposure. These results demonstrate that a single sequence of intermittent bright light pulses can phase delay the human circadian pacemaker and show that intermittent pulses have a greater resetting efficacy on a per minute basis than does continuous exposure.     

Fluoxetine subsensitizes a nicotinic mechanism involved in the regulation of core temperature

Fluoxetine HCl, 10 mg/kg ip, twice daily produced subsensitivity to the hypothermic effects of nicotine (base), 1 mg/kg ip, after 1 (p less than 0.02) and 2 (p less than 0.002) weeks of treatment. Phenelzine sulfate, desipramine HCl and bright artificial light produced the same effect. The capacity of three chemically distinct classes of antidepressants and bright artificial light (a treatment for seasonal depression) to produce this result suggests that effects on nicotinic mechanisms may be involved in the mechanism of action of these treatments.     

Quantal melatonin suppression by exposure to low intensity light in man

Plasma melatonin concentrations were examined following three relatively low intensities of artificial light. Six normal, healthy control subjects were all exposed to (a) 200 lux, (b) 400 lux and (c) 600 lux for a three hour duration from midnight to 0300 h. Blood was also collected on a control night where light intensity was less than 10 lux throughout. Significant suppression of melatonin was observed following light of 400 lux and 600 lux intensity when compared to the control night (p less than 0.05; Mann-Whitney U-test). 200 lux light did not produce a statistically significant melatonin suppression when compared with control samples. Each light intensity produced its own individual maximal melatonin suppression by one hour of exposure. Increased duration of exposure to the light had no further influence on melatonin plasma concentrations. These data confirm a dose response relationship between light and melatonin suppression, and indicate that there is no reciprocal relationship between the effects of light intensity and the duration of exposure on maximal melatonin suppression in man.     

Effect of varying light intensity on maximal power production and selected metabolic variables

This study was designed to examine the effect of exposure to two levels of light intensity (bright; 5000 lux, dim; 50 lux) prior to supramaximal cycle exercise on performance and metabolic alterations. The exercise was performed after bright and dim light exposure for 90 minutes. Ten male long-distance runners volunteered to take part in the study. They performed 45-sec supramaximal exercise using a cycle ergometer in a 500-lux. Mean power output was measured during the exercise. Lactate and ammonia in the blood and epinephrine and norepinephrine concentrations in plasma were measured at rest immediately after bright and dim light exposures and after the exercise. Bright and dim light exposure prior to exercise did not significantly affect the power output during the exercise. Blood glucose concentration immediately after exercise and plasma epinephrine during the resting period were significantly lower after bright light exposure compared with dim light exposure (p < 0.05). No significant difference was found in blood lactate, ammonia, or plasma norepinephrine levels after exercise following bright and dim light exposures. This study demonstrated that bright light stimulation prior to supramaximal exercise decreases glucose and epinephrine levels, but is not related to physical performance.     

Suppression of nocturnal plasma melatonin and 6-sulphatoxymelatonin by bright and dim light in man

Previous studies have shown that bright light (2500 lux) suppresses nocturnal secretion of melatonin, while dim light (500 lux) has little or no effect. We have studied the effect of varying intensities of light on 5 normal male volunteers (age 18-28). The experiment was divided into 3 parts which took place at weekly intervals. Subjects remained under artificial light (fluorescent strip 150-250 lux) between 2000 h-2300 h, they then retired to bed in darkness. On each occasion, between 0030 h and 0100 h, the subjects were required to get up and were treated with light of different intensities; (a) less than 1 lux, (b) 300 lux and (c) 2500 lux respectively. Subjects returned to bed in darkness until 0700 h. Blood was sampled hourly from 2000 h-1000 h with additional samples at 2330 h, 0015 h, 0030 h, 0045 h, 0115 h and 0130 h. Plasma melatonin and 6-sulphatoxymelatonin (aMT6s), the major melatonin metabolite, were measured by radioimmunoassay. Dim (300 lux) and bright (2500 lux) light, both significantly suppressed melatonin levels compared to less than 1 lux (P less than 0.05 and P less than 0.01 respectively) at the following time points 0100 h, 0115 h and 0130 h. One subject did not show suppression with 300 lux. There was also a significant suppression of aMT6s levels, compared to less than 1 lux, after both 300 lux and 2500 lux at 0115 h (P less than 0.05, P less than 0.01), 0130 h (P less than 0.01, P less than 0.01) and 0200 h (P less than 0.01, P less than 0.001) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bright Light Exposure During the Daytime Affects Circadian Rhythms of Urinary Melatonin and Salivary Immunoglobulin A

The effects of bright light exposure during the daytime on circadian urinary melatonin and salivary immunoglobulin A (IgA) rhythms were investigated in an environmental chamber controlled at a global temperature of 27°C ± 0.2°C and a relative humidity of 60% ± 5%. Seven diurnally active healthy females were studied twice, in bright and dim light conditions. Bright light of 5000 lux was provided by placing fluorescent lamps about 1 meter in front of the subjects during the daytime exposure (06:30-19:30) from 06:30 on day 1 to 10:30 on day 3. Dim light was controlled at 200 lux, and the subjects were allowed to sleep from 22:30 to 06:30 under both light exposure conditions. Urine and saliva were collected at 4h intervals for assessing melatonin and IgA. Melatonin excretion in the urine was significantly greater during the nighttime (i.e., at 06:30 on day 1 and at 02:30 on day 2) after the bright light condition than during the dim light condition. Furthermore, the concentration and the amount of salivary IgA tended to be higher in the bright light than in the dim light condition, especially during the nighttime. Also, salivary IgA concentration and the total amount secreted in the saliva were significantly positively correlated with urinary melatonin. These results are consistent with the hypothesis that bright light exposure during the daytime enhances the nocturnal melatonin increase and activates the mucosal immune response.     

Effect of evening exposure to dim or bright light on the digestion of carbohydrate in the supper meal

In a previous study we found that daytime exposure to bright as compared to dim light exerted a beneficial effect on the digestion of the evening meal. This finding prompted us to examine whether the digestion of the evening meal is also affected by evening light intensity. Subjects lived in light of 200 lux during the daytime (08:00-17:00 h) and took their evening meal at 17:00 h under 20 lux (evening dim-light condition: 17:00-02:00 h) or 2000 lux (evening bright-light condition: 17:00-02:00 h) until retiring at 02:00 h. Assessment of carbohydrate digestion of the evening meal was accomplished by a breath hydrogen test that is indicative of the malabsorption of dietary carbohydrate. Hydrogen excretion in the breath in the evening under the dim-light condition was significantly less than under the bright-light condition (p < 0.05). This finding is the opposite to that obtained in previous experiments in which subjects were exposed to the different intensities of light during the daytime, and indicates that the exposure to dim light in the evening exerts a better effect on carbohydrate digestion in the evening meal than does the exposure to bright light.     

Less exposure to daily ambient light in winter increases sensitivity of melatonin to light suppression

This study was carried out to examine the seasonal difference in the magnitude of the suppression of melatonin secretion induced by exposure to light in the late evening. The study was carried out in Akita (39 degrees North, 140 degrees East), in the northern part of Japan, where the duration of sunshine in winter is the shortest. Ten healthy male university students (mean age: 21.9+/-1.2 yrs) volunteered to participate twice in the study in winter (from January to February) and summer (from June to July) 2004. According to Japanese meteorological data, the duration of sunshine in Akita in the winter (50.5 h/month) is approximately one-third of that in summer (159.7 h/month). Beginning one week prior to the start of the experiment, the level of daily ambient light to which each subject was exposed was recorded every minute using a small light sensor that was attached to the subject's wrist. In the first experiment, saliva samples were collected every hour over a period of 24 h in a dark experimental room (<15 lux) to determine peak salivary melatonin concentration. The second experiment was conducted after the first experiment to determine the percentage of melatonin suppression induced by exposure to light. The starting time of exposure to light was set 2 h before the time of peak salivary melatonin concentration detected in the first experiment. The subjects were exposed to light (1000 lux) for 2 h using white fluorescent lamps (4200 K). The percentage of suppression of melatonin by light was calculated on the basis of the melatonin concentration determined before the start of exposure to light. The percentage of suppression of melatonin 2 h after the start of exposure to light was significantly greater in winter (66.6+/-18.4%) than summer (37.2+/-33.2%), p<0.01). The integrated level of daily ambient light from rising time to bedtime in summer was approximately twice that in winter. The results suggest that the increase in suppression of melatonin by light in winter is caused by less exposure to daily ambient light.     

Influence of light intensities on dressing behavior in elderly people

With civilized environments in modern society, since the people tend to depend more on artificial illumination than on natural illumination which makes less discrepancy between day and night life, clarifying the relationship between human life and illumination is necessary. In our previous studies, we found that the subjects dressed faster with thicker clothing in the morning than in the evening when the room temperature decreased from 30 degrees C to 15 degrees C over 1 hour. We considered these results in terms of load error between the actual and set-point values in the core temperature. The present study was designed to examine the effect of bright light (3,000 lx)/dim light (50 lx) exposure (09:30 h-14:30 h) on dressing behavior and thermoregulatory responses in the elderly people during the afternoon cold exposure. Five female subjects were instructed to dress to feel comfortable when the room temperature was decreased from 30 degrees C to 15 degrees C (15:00 h-17:00 h). The subjects felt cooler and dressed more quickly with thicker clothing after dim light exposure, it is conceivable that the set-point value of core temperature is reduced under the bright light condition. We discussed these results in terms of the establishment of set-point values in the core temperature at bright light condition. If the set-point of the core temperature is lower in the bright than in the dim light condition in present experiment, the dressing behavior with thinner clothing in the bright light condition is advantageous, since it enables the core temperature to reach its set-point value more easily.     

The effects of bright light and nighttime melatonin administration on cardiac activity

Although melatonin has an important physiological role in the facilitation of sleep, its precise mechanism of action is not clear. To investigate the potential contribution of melatonin to influence cardiac autonomic activity in the evening, 16 young healthy subjects participated in a repeated measures design where cardiac autonomic activity, heart rate and blood pressure were examined during three experimental conditions. An initial baseline condition involved dim light exposure (< 10 lux), permitting the normal nocturnal rise in endogenous melatonin. In other sessions, subjects were exposed to bright light (> 3000 lux) to suppress melatonin secretion and administered a placebo or melatonin (5 mg) capsule at the estimated time of increase in endogenous melatonin (wake time + 14 hours). Heart rate, pre-ejection period (a measure of cardiac sympathetic activity) and respiratory sinus arrhythmia (a measure of parasympathetic activity) were not significantly altered in response to the three melatonin levels. While melatonin had no effect on diastolic blood pressure, systolic blood pressure was maximally decreased by 6 +/- 1.93 mmHg (mean +/- SEM, p < 0.005) 150 minutes after exogenous melatonin. The results indicate that melatonin does not directly modulate cardiac autonomic activity, but may rather act directly on the cardiovascular system.     

Influence of bright light exposure for several hours during the daytime on cutaneous vasodilatation and local sweating induced by an exercise heat load

The aim of the present study was to investigate the effect of exposure to differing light intensities for several hours during the daytime on the cutaneous vasodilatation and local forearm sweat rate induced by exercise. Seven healthy female subjects were exposed to bright light of 6000 lux (bright) or dim light of 100 lux (dim) during the daytime between 0900 hours to 1330 hours, followed by exposure to 150 lux until the test was over at 1600 hours. They spent their time in neutral conditions (29°C, 40% relative humidity) from 0900 hours to 1500 hours, and then exercised on a cycle ergometer for 30 min at 50% maximal physical work capacity. Average tympanic temparatures were significantly lower in bright than in dim from 1133 hours to 1430 hours. The onset of cutaneous vasodilatation and local forearm sweating occurred at significantly lower tympanic temperature (T _ty) during exercise after bright than after dim. After exercise, the cessation of forearm sweating and the rapid change of skin blood flow occurred at significantly lower T _ty after bright than after dim. It was concluded that exposure to bright light over several hours during the daytime could reduce T _ty and shift the threshold T _ty for cutaneous vasodilatation and forearm sweating to a lower level. Accepted: 30 March 1998     

Parietalectomy does not affect testicular growth in photoregulating lizards

The testicular response of male anoles maintained at a constant 32 degrees C was similar in both parietalectomized and sham-parietalectomized lizards exposed to either constant light (40 lux intensity) or to photic gradients (40-300 lux). The results support the hypothesis that the acceleration of gonadal growth in parietalectomized lizards noted by others depends on the ability of lizards to self-regulate exposure to thermal, but not photic, stimuli.     

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     

Thermoregulatory responses in humans during exercise after exposure to two different light intensities

The effects after exposure to two different light intensities (dim, 50 lx and bright, 5000 lx) on thermoregulatory responses during exercise in a climatic chamber (27 degrees C, 60% relative humidity) were studied in nine untrained female subjects, aged 19-22 years. The subjects were in either the dim or bright light intensities from 0600 hours to 1200 hours. They were then instructed to exercise on a cycle ergometer at an intensity of 60% maximal oxygen uptake from 1200 hours to 1300 hours in a light intensity of 500 Ix. The main results can be summarized as follows. Firstly, exercise-induced increases of core temperature were significantly smaller, after exposure to the bright than after the dim light intensities, although both tests were performed in the same light intensity. Secondly, body mass loss after exercise was significantly greater after exposure to the bright light intensity. Thirdly, an increase in salivary lactic acid during exercise was significantly lower after the bright intensity. Fourthly although the salivary melatonin level was not different between the two light intensities both before and after the exercise, it increased significantly during exercise only after the bright intensity. These results are discussed in terms of the establishment of a lower set-point in the core temperature after exposure to a bright light intensity.     

The influence of the two different light intensities duringthe daytime on the colon motility in patients with irritable bowel syndrome (IBS): a preliminary report

Irritable bowel syndrome (IBS) is the most frequent functional disorder of the gastrointestinal tract, with great economical impact. The etiology and pathogenesis of the disease are unclear. Among patients seeking medical attention for IBS, 70 - 90% have psychiatric co-morbidity, most commonly major depression. In this study we test the influence of bright light on colon motility and subjectively felt symptoms. Eight IBS patients participated in the experiment. The passage rate was evaluated twice for every person: (1) after three days of exposure to bright light -3000 lux (from 8:00 to 18:00), (2) after three days exposure to dim light -100 lux (from 8:00 to 18:00). The comparison of colonic time in IBS patients point to differences in the elimination of markers, depending on experimental light conditions. After bright light conditions a tendency is observed to slower elimination of markers in the IBS-diarrhoea patients, and to a quicker elimination in the IBS-constipated patients. According to subjective feeling, all IBS patients reported an improvement in bowel function and relief of pain after bright but not after dim light application. Results of this preliminary study suggest that phototherapy might be a valuable addition to the conventional treatment of IBS.     

Bright-light mask treatment of delayed sleep phase syndrome

We treated delayed sleep phase syndrome (DSPS) with an illuminated mask that provides light through closed eyelids during sleep. Volunteers received either bright white light (2,700 lux, n = 28) or dim red light placebo (0.1 lux, n = 26) for 26 days at home. Mask lights were turned on (< 0.01 lux) 4 h before arising, ramped up for 1 h, and remained on at full brightness until arising. Volunteers also attempted to systematically advance sleep time, avoid naps, and avoid evening bright light. The light mask was well tolerated and produced little sleep disturbance. The acrophase of urinary 6-sulphatoxymelatonin (6-SMT) excretion advanced significantly from baseline in the bright group (p < 0.0006) and not in the dim group, but final phases were not significantly earlier in the bright group (ANCOVA ns). Bright treatment did produce significantly earlier phases, however, among volunteers whose baseline 6-SMT acrophase was later than the median of 0602 h (bright shift: 0732-0554 h, p < 0.0009; dim shift: 0746-0717 h, ns; ANCOVA p = 0.03). In this subgroup, sleep onset advanced significantly only with bright but not dim treatment (sleep onset shift: bright 0306-0145 h, p < 0.0002; dim 0229-0211 h, ns; ANCOVA p < .05). Despite equal expectations at baseline, participants rated bright treatment as more effective than dim treatment (p < 0.04). We conclude that bright-light mask treatment advances circadian phase and provides clinical benefit in DSPS individuals whose initial circadian delay is relatively severe.     

Effect of Evening Exposure to Dim or Bright Light on the Digestion of Carbohydrate in the Supper Meal

In a previous study we found that daytime exposure to bright as compared to dim light exerted a beneficial effect on the digestion of the evening meal. This finding prompted us to examine whether the digestion of the evening meal is also affected by evening light intensity. Subjects lived in light of 200 lux during the daytime (08:00–17:00 h) and took their evening meal at 17:00 h under 20 lux (evening dim‐light condition: 17:00–02:00 h) or 2000 lux (evening bright‐light condition: 17:00–02:00 h) until retiring at 02:00 h. Assessment of carbohydrate digestion of the evening meal was accomplished by a breath hydrogen test that is indicative of the malabsorption of dietary carbohydrate. Hydrogen excretion in the breath in the evening under the dim‐light condition was significantly less than under the bright‐light condition (p < 0.05). This finding is the opposite to that obtained in previous experiments in which subjects were exposed to the different intensities of light during the daytime, and indicates that the exposure to dim light in the evening exerts a better effect on carbohydrate digestion in the evening meal than does the exposure to bright light.     

Red white and blue – bright light effects in a diurnal rodent model for seasonal affective disorder

Despite the common use of bright light exposure for treatment of seasonal affective disorder (SAD), the underlying biology of the therapeutic effect is not clear. Moreover, there is a debate regarding the most efficacious wavelength of light for treatment. Whereas according to the traditional approach full-spectrum light is used, recent studies suggest that the critical wavelengths are within the range of blue light (460 and 484 nm). Our previous work shows that when diurnal rodents are maintained under short photoperiod they develop depression- and anxiety-like behavioral phenotype that is ameliorated by treatment with wide-spectrum bright light exposure (2500 lux at the cage, 5000 K). Our current study compares the effect of bright wide-spectrum (3,000 lux, wavelength 420- 780 nm, 5487 K), blue (1,300 lux, wavelength 420-530 nm) and red light (1,300 lux, wavelength range 600-780 nm) exposure in the fat sand rat (Psammomys Obesus) model of SAD. We report results of experiments with six groups of sand rats that were kept under various photoperiods and light treatments, and subjected to behavioral tests related to emotions: forced swim test, elevated plus maze and social interactions. Exposure to either intense wide-spectrum white light or to blue light equally ameliorated depression-like behavior whereas red light had no effect. Bright wide-spectrum white light treatment had no effect on animals maintained under neutral photoperiod, meaning that light exposure was only effective in the pathological-like state. The resemblance between the effects of bright white light and blue light suggests that intrinsically photosensitive retinal ganglion cells (ipRGCs) are involved in the underlying biology of SAD and light therapy.     

Circadian adaptation to night-shift work by judicious light and darkness exposure

In this combined field and laboratory investigation, the authors tested the efficacy of an intervention designed to promote circadian adaptation to night-shift work. Fifteen nurses working permanent night schedules (> or = 8 shifts/ 15 days) were recruited from area hospitals. Following avacation period of > or = 10 days on a regular daytime schedule, workers were admitted to the laboratory for the assessment of circadian phase via a 36-h constant routine. They returned to work approximately 12 night shifts on their regular schedules under one of two conditions. Treatment group workers (n = 10, mean age +/- SD = 41.7 +/- 8.8 years) received an intervention including 6 h of intermittent bright-light exposure in the workplace (approximately 3,243 lux) and shielding from bright morning outdoor light with tinted goggles (15% visual light transmission). Control group workers (n = 9, mean age +/- SD = 42.0 +/- 7.2 years) were observed in their habitual work environments. On work days, participants maintained regular sleep/wake schedules including a single 8-h sleep/darkness episode beginning 2 h after the end of the night shift. A second 36-h constant routine was performed following the series of night shifts. In the presence of the intervention, circadian rhythms of core body temperature and salivary melatonin cycles were delayed by an average (+/- SEM) of -9.32 +/- 1.06 h and -11.31 +/- 1.13 h, respectively. These were significantly greater than the phase delays of -4.09 +/- 1.94 h and -5.08 +/- 2.32 h displayed by the control group (p = 0.03 and p = 0.02, respectively). The phase angle between circadian markers and the shifted schedule was reestablished to its baseline position only in the treatment group of workers. These results support the efficacy of a practical intervention for promoting circadian adaptation to night-shift work under field conditions. They also underline the importance of controlling the overall pattern of exposure to light and darkness in circadian adaptation to shifted sleep/wake schedules.