Effect of light treatment on sleep and circadian rhythms in demented nursing home patients

OBJECTIVES: To determine whether fragmented sleep in nursing home patients would improve with increased exposure to bright light. DESIGN: Randomized controlled trial. SETTING: Two San Diego-area nursing homes. PARTICIPANTS: Seventy-seven (58 women, 19 men) nursing home residents participated. Mean age +/- standard deviation was 85.7 +/- 7.3 (range 60-100) and mean Mini-Mental State Examination was 12.8 +/- 8.8 (range 0-30). INTERVENTIONS: Participants were assigned to one of four treatments: evening bright light, morning bright light, daytime sleep restriction, or evening dim red light. MEASUREMENTS: Improvement in nighttime sleep quality, daytime alertness, and circadian activity rhythm parameters. RESULTS: There were no improvements in nighttime sleep or daytime alertness in any of the treatment groups. Morning bright light delayed the peak of the activity rhythm (acrophase) and increased the mean activity level (mesor). In addition, subjects in the morning bright light group had improved activity rhythmicity during the 10 days of treatment. CONCLUSION: Increasing exposure to morning bright light delayed the acrophase of the activity rhythm and made the circadian rhythm more robust. These changes have the potential to be clinically beneficial because it may be easier to provide nursing care to patients whose circadian activity patterns are more socially acceptable.     

The spectral composition of evening light and individual differences in the suppression of melatonin and delay of sleep in humans

The effect of light on circadian rhythms and sleep is mediated by a multi-component photoreceptive system of rods, cones and melanopsin-expressing intrinsically photosensitive retinal ganglion cells. The intensity and spectral sensitivity characteristics of this system are to be fully determined. Whether the intensity and spectral composition of light exposure at home in the evening is such that it delays circadian rhythms and sleep also remains to be established. We monitored light exposure at home during 6-8wk and assessed light effects on sleep and circadian rhythms in the laboratory. Twenty-two women and men (23.1±4.7yr) participated in a six-way, cross-over design using polychromatic light conditions relevant to the light exposure at home, but with reduced, intermediate or enhanced efficacy with respect to the photopic and melanopsin systems. The evening rise of melatonin, sleepiness and EEG-assessed sleep onset varied significantly (P<0.01) across the light conditions, and these effects appeared to be largely mediated by the melanopsin, rather than the photopic system. Moreover, there were individual differences in the sensitivity to the disruptive effect of light on melatonin, which were robust against experimental manipulations (intra-class correlation=0.44). The data show that light at home in the evening affects circadian physiology and imply that the spectral composition of artificial light can be modified to minimize this disruptive effect on sleep and circadian rhythms. These findings have implications for our understanding of the contribution of artificial light exposure to sleep and circadian rhythm disorders such as delayed sleep phase disorder.     

Circadian rhythms of plasma melatonin in the Adelie penguin (Pygoscelis adeliae) in constant dim light and artificial photoperiods

The response of plasma melatonin in Adelie penguins (Pygoscelis adeliae) to constant dim light and to light/dark cycles was measured to determine the capacity of the pineal gland to secrete melatonin after exposure to continuous daylight for 2 months. Penguins were moved in mid-summer from the natural photoperiod to either constant dim light (n = 10), to a 12L:12D light/dark cycle (n = 5), or to a 12L:12D light/dark cycle with a 30 min light pulse (50-155 lux) on the third (n = 4) or sixth (n = 5) "night." Blood samples were collected regularly through cannulae for up to 33 h. The birds in dim light were sampled after 2 days, with samples obtained over at least 24 h from 7 birds. Three of these birds had melatonin rhythms (peak levels 66.7-130.2 pg/ml) whereas the other 4 birds had constant low levels (less than 44 pg/ml). The phase of the rhythm was similar for all 3 birds. This is consistent with the pacemaker that regulates the circadian rhythm of melatonin secretion being entrained to a period of 24 h when the penguins were exposed to the natural photoperiod. Mean melatonin levels (42.7 +/- 2.5 pg/ml) were elevated compared to those previously reported in penguins under natural daylight. All penguins held under a 12L:12D light/dark cycle had melatonin rhythms. The phase and form of these rhythms were similar to those reported for other birds, and they appeared to be circadian rhythms entrained by the light/dark cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evening melatonin and bright light administration induce additive phase shifts in dim light melatonin onset

In healthy young men, administration of a single light pulse (5000 lux for 3 hr) or a single melatonin pill (5 mg) at 20:40 hr under controlled constant routine conditions of <10 lux, yielded a phase delay and a phase advance, respectively, in the circadian marker of dim light melatonin onset 24 hr later. Phase shifts after combining the two interventions were additive. Melatonin suppression is not necessary for a phase shift by light, and melatonin is not a 'weak' Zeitgeber relative to bright light when ambient lighting is strictly controlled.     

Melanopic illuminance defines the magnitude of human circadian light responses under a wide range of conditions

Ocular light drives a range of nonvisual responses in humans including suppression of melatonin secretion and circadian phase resetting. These responses are driven by intrinsically photosensitive retinal ganglion cells (ipRGCs) which combine intrinsic, melanopsin-based, phototransduction with extrinsic rod/cone-mediated signals. As a result of this arrangement, it has remained unclear how best to quantify light to predict its nonvisual effects. To address this, we analysed data from nineteen different laboratory studies that measured melatonin suppression, circadian phase resetting and/or alerting responses in humans to a wide array of stimulus types, intensities and durations with or without pupil dilation. Using newly established SI-compliant metrics to quantify ipRGC-influenced responses to light, we show that melanopic illuminance consistently provides the best available predictor for responses of the human circadian system. In almost all cases, melanopic illuminance is able to fully account for differences in sensitivity to stimuli of varying spectral composition, acting to drive responses that track variations in illumination characteristic of those encountered over civil twilight (~1-1000 lux melanopic equivalent daylight illuminance). Collectively, our data demonstrate widespread utility of melanopic illuminance as a metric for predicting the circadian impact of environmental illumination. These data therefore provide strong support for the use of melanopic illuminance as the basis for guidelines that seek to regulate light exposure to benefit human health and to inform future lighting design.     

Epidemiological evidence for the links between sleep, circadian rhythms and metabolism

Epidemiological data reveal parallel trends of decreasing sleep duration and increases in metabolic disorders such as obesity, diabetes and hypertension. There is growing evidence that these trends are mechanistically related. The seasonal expression of the thrifty genotype provides a conceptual framework to connect circadian and circannual rhythms, sleep and metabolism. Experimental studies have shown sleep deprivation to decrease leptin, increase ghrelin, increase appetite, compromise insulin sensitivity and raise blood pressure. Habitually short sleep durations could lead to insulin resistance by increasing sympathetic nervous system activity, raising evening cortisol levels and decreasing cerebral glucose utilization that over time could compromise β-cell function and lead to diabetes. Prolonged short sleep durations could lead to hypertension through raised 24-h blood pressure and increased salt retention resulting in structural adaptations and the entrainment of the cardiovascular system to operate at an elevated pressure equilibrium. Cross-sectional and longitudinal epidemiological studies have shown associations between short sleep duration and obesity, diabetes and hypertension. If metabolic changes resulting from sleep restriction function to increase body weight, insulin resistance and blood pressure then interventions designed to increase the amount and improve the quality of sleep could serve as treatments and as primary preventative measures for metabolic disorders.     

High-intensity environmental light in dementia: effect on sleep and activity

OBJECTIVES: To determine whether high-intensity ambient light in public areas of long-term care facilities will improve sleeping patterns and circadian rhythms of persons with dementia. DESIGN: A cluster-unit crossover intervention trial involving four conditions: morning bright light, evening bright light, all-day bright light, and minimum standard light. SETTING: The common areas of two geriatric units in a psychiatric hospital and a dementia-specific residential care facility. PARTICIPANTS: Sixty-six older adults with dementia. INTERVENTION: Ambient bright light of approximately 2,500 lux, delivered through a low-glare lighting system installed in the dining and activity areas. Participant exposure averaged 2.5 to 3.0 hours for the morning and evening interventions and 8.4 hours for the all-day intervention. MEASUREMENTS: Nighttime sleep using wrist actigraphy and daytime activity using nonobtrusive daytime observations. RESULTS: Night-time sleep increased significantly in participants exposed to morning and all-day light, with the increase most prominent in participants with severe or very severe dementia (mean increase 16 minutes (P=.008) for morning, and 14 minutes (P=.01) for all-day). Morning light produced a mean phase advance of 29 minutes (P=.02) and evening light a mean phase delay of 15 minutes (P=.06). Effects on daytime sleepiness were inconsistent, and the number of sleep bouts, mesor, amplitude, intradaily variability, and interdaily stability were not significantly different, indicating that the overall strength of day and night activity rhythms did not change significantly under any treatment condition. CONCLUSION: Bright light appears to have a modest but measurable effect on sleep in this population, and ambient light may be preferable to stationary devices such as light boxes.     

Phase-shifting effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin in the chick pineal gland

In the chick pineal gland, 5-methoxytryptophol and melatonin concentrations fluctuate in a rhythmic manner. These rhythms are circadian in nature persisting in constant darkness and have opposite phases. Acute exposure of chicks to white light (30 lux for 5, 10, 20, and 30 min) at night increased the amount of pineal 5-methoxytryptophol and decreased pineal melatonin content. A 6 hr pulse of light (100 lux) applied early in the subjective night (CT12-CT18) caused a delay in the phase of the circadian rhythms of 5-methoxytryptophol and melatonin by 3.7 and 4.5 h, respectively, compared to untreated controls. When the 6 hr light pulse was given during the late subjective night (C18 CT24) it advanced the phase of the 5-methoxytryptophol and melatonin rhythms by 8.1 and 11.9 h, respectively. In the chick pineal the phase-advancing effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin were more pronounced than the phase-delaying effects. Our results provide the first evidence that light is capable of phase shifting the 5-methoxytryptophol rhythm in a manner similar to its action on the melatonin rhythm.     

The validity and feasibility of saliva melatonin assessment in the elderly

Recent work in young and middle-aged subjects suggests that melatonin levels in saliva may represent a viable alternative to serum melatonin measurement. We hypothesized that it may be a valid measure of melatonin levels in older adults as well, but features unique to the elderly may limit its utility. To study this, subjects were admitted to an academic medical center where saliva and serum specimens were collected concurrently in dim light conditions during a 14-hr overnight study period and analyzed for melatonin levels with radioimmunoassays (RIAs). Eighty-five subjects over the age of 65 with a broad range of medical conditions participated in the study. Subjects with dementia, depression and anemia were excluded. We found that saliva volume was inadequate for analysis (<200 microL) in 23.6% of specimens, with the majority of inadequate volume specimens occurring after midnight and inadequate specimens occurring more frequently in females than in males. The correlation coefficient for saliva melatonin and serum melatonin was r = 0.659 (Spearman, P < 0.001), and r = 0.466 for saliva dim light melatonin onset (DLMO) and serum DLMO. Saliva melatonin levels were 30.9% of serum melatonin levels, with a wide range of ratios noted between subjects. Overall melatonin levels influenced both the correlation and ratio of saliva melatonin to serum melatonin; higher correlations and lower ratios were noted when melatonin levels were high. Saliva specimens provide an economical and practical method for melatonin assessment, however, in older adults, issues such as hyposalivation and low melatonin levels limit the feasibility and validity, respectively, of saliva melatonin.     

The effects of prior light history on the suppression of melatonin by light in humans

We investigated the impact of light exposure history on light sensitivity in humans, as assessed by the magnitude of the suppression of melatonin secretion by nocturnal light. The hypothesis was that following a week of increased daytime bright-light exposure, subjects would become less sensitive to light, and that after a week of restriction to dimmer light they would become more sensitive. During the bright week, subjects (n = 12) obtained 4.3 +/- 0.4 hr of bright light per day (by going outside and using light boxes indoors). During the dim week, they wore dark goggles (about 2% light transmission) when outside during daylight and spent 1.4 +/- 0.9 hr per day outside. Saliva samples were obtained every 30 min for 7 hr in dim light (<15 lux) on two consecutive nights (baseline and test night) at the end of each week. On the test night, 500 lux was presented for 3 hr in the middle of the collection period to suppress melatonin. There was significantly more suppression after the dim week compared with after the bright week (to 53 versus 41% of the baseline night values, P < 0.05). However, there were large individual differences, and the difference between the bright and dim weeks was most pronounced in seven of the 12 subjects. Possible reasons for these individual differences are discussed, including the possibility that 1 wk was not long enough to change light sensitivity in some subjects. In conclusion, this study suggests that the circadian system's sensitivity to light can be affected by a recent change in light history.     

From the Cover: The endogenous circadian system worsens asthma at night independent of sleep and other daily behavioral or environmental cycles

Asthma often worsens at night. To determine if the endogenous circadian system contributes to the nocturnal worsening of asthma, independent of sleep and other behavioral and environmental day/night cycles, we studied patients with asthma (without steroid use) over 3 wk in an ambulatory setting (with combined circadian, environmental, and behavioral effects) and across the circadian cycle in two complementary laboratory protocols performed in dim light, which separated circadian from environmental and behavioral effects: 1) a 38-h “constant routine,” with continuous wakefulness, constant posture, 2-hourly isocaloric snacks, and 2) a 196-h “forced desynchrony” incorporating seven identical recurring 28-h sleep/wake cycles with all behaviors evenly scheduled across the circadian cycle. Indices of pulmonary function varied across the day in the ambulatory setting, and both laboratory protocols revealed significant circadian rhythms, with lowest function during the biological night, around 4:00 AM, uncovering a nocturnal exacerbation of asthma usually unnoticed or hidden by the presence of sleep. We also discovered a circadian rhythm in symptom-based rescue bronchodilator use (β2-adrenergic agonist inhaler) whereby inhaler use was four times more likely during the circadian night than day. There were additive influences on asthma from the circadian system plus sleep and other behavioral or environmental effects. Individuals with the lowest average pulmonary function tended to have the largest daily circadian variations and the largest behavioral cycle effects on asthma. When sleep was modeled to occur at night, the summed circadian, behavioral/environmental cycle effects almost perfectly matched the ambulatory data. Thus, the circadian system contributes to the common nocturnal worsening of asthma, implying that internal biological time should be considered for optimal therapy.

Asthma is characterized by bronchial hyperreactivity leading to airway inflammation, bronchoconstriction, and symptoms of “chest tightness.” It has been recognized for hundreds of years that asthma severity generally increases at night, producing what had historically been termed “nocturnal asthma.” For instance, in 1698, the physician Sir John Floyer recognized from his own experience that “at first waking, about one or two of the Clock in the Night, the Fit of the Asthma more evidently begins” (1). Nocturnal worsening of asthma occurs in as many as 75% of patients with asthma, equating to 20 million people in the United States alone (2–6). The variation across the day and night in peak expiratory flow (PEF) can be as much as 50% (7, 8). Also, the highest rate of asthma exacerbations leading to respiratory failure or death occurs across the night (3, 9, 10). Therefore, understanding the mechanisms underlying the daily variability in asthma severity could have major diagnostic and therapeutic implications.Behavioral and environmental factors are known to affect asthma severity, including exercise, air temperature, pollution, the sleep/wake cycle (11), changes in posture (12), and the sleeping environment (13). However, it is also possible that the endogenous circadian timing system contributes to nocturnal worsening of asthma (14). The circadian system—composed of the central circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus and circadian oscillators in most organs and tissues of the body—orchestrates ∼24-h rhythms in physiology and behavior (15). This endogenous timing system may influence the pulmonary and inflammatory system via the autonomic nervous system (16), humoral factors (17), and/or local molecular clocks (18, 19).We tested the hypothesis that the circadian system, independent of sleep and other behavioral and environmental factors, contributes to the nocturnal worsening of asthma in humans.     

Influence of the pineal gland and circadian rhythms in circulating levels of thyroid hormones of male hamsters

Thyroxin (T4) and triiodothyronine (T3) were measured by radioimmunoassay in serum of hamsters sacrificed at 4-hr intervals throughout the daily light-dark cycle (14L/10D). Both T4 and T3 concentrations increased significantly during the L period of the daily cycle and decreased during the D period of the cycle; A.M. versus P.M. differences in free thyroxin indices (FTI) were also studied using the T4 and T3 uptake assays of Nuclear Medical Laboratories (Dallas, Texas). The free thyroxin index was significantly greater in serum samples of hamsters sacrificed at 7 P.M. than at 7 A.M. (lights on at 6:30 A.M.). Serum taken at 7 P.M. had less unsaturated binding sites than serum taken at 7 A.M. No significant A.M. versus P.M. differences in free thyroxin index were found in blind hamsters, although blind hamsters had significantly lower T4 and FTI than controls. Placing melatonin in the drinking water at a dose of 80 μg/ml did not significantly influence hormone levels. The greatest difference in hormone concentrations between control and blinded hamsters was found in P.M. samples. Blind hamsters had FTIs that were 48% of P.M. controls. Pinealectomy prevented the effects of blinding on T4 levels and FTIs.     

Classification of circadian pain rhythms and pain characteristics in chronic pain patients: An observational study

This study aimed to perform cluster analysis in patients with chronic pain to extract groups with similar circadian rhythms and compare neuropathic pain and psychological factors among these groups to identify differences in pain-related outcomes. A total of 63 community-dwellers with pain lasting at least 3 months and Numerical Rating Scale scores of ≥2 were recruited from 3 medical institutions. Their pain circadian rhythms were evaluated over 7 days by measuring pain intensity at 6-time points per day using a 10-cm visual analog scale. Cluster analysis was performed using 6 variables with standardized visual analog scale values at 6-time points for individual participants to extract groups with similar pain circadian rhythms. The results of the Neuropathic Pain Symptom Inventory and psychological evaluations in each group were compared using the Kruskal–Wallis test. The results revealed 3 clusters with different circadian rhythms of pain. The total and evoked pain subscale Neuropathic Pain Symptom Inventory scores differed among the 3 clusters. The results suggest that a thorough understanding of circadian pain rhythms in chronic pain patients may facilitate the performance of activities of daily living and physical exercise from the perspective of pain management.     

A unified model of melatonin, 6‐sulfatoxymelatonin,and sleep dynamics

A biophysical model of the key aspects of melatonin synthesis and excretion has been developed, which is able to predict experimental dynamics of melatonin in plasma and saliva, and of its urinary metabolite 6‐sulfatoxymelatonin (aMT6s). This new model is coupled to an established model of arousal dynamics, which predicts sleep and circadian dynamics based on light exposure and times of wakefulness. The combined model thus predicts melatonin levels over the sleep‐wake/dark‐light cycle and enables prediction of melatonin‐based circadian phase markers, such as dim light melatonin onset (DLMO) and aMT6s acrophase under conditions of normal sleep and circadian misalignment. The model is calibrated and tested against group average data from 10 published experimental studies and is found to reproduce quantitatively the key dynamics of melatonin and aMT6s, including the timing of release and amplitude, as well as response to controlled lighting and shift work.     

Age-related disruptions of circadian rhythm and memory in the senescence-accelerated mouse (SAMP8)

Common complaints of the elderly involve impaired cognitive abilities, such as loss of memory and inability to attend. Although much research has been devoted to these cognitive impairments, other factors such as disrupted sleep patterns and increased daytime drowsiness may contribute indirectly to impaired cognitive abilities. Disrupted sleep–wake cycles may be the result of age-related changes to the internal (circadian) clock. In this article, we review recent research on aging and circadian rhythms with a focus on the senescence-accelerated mouse (SAM) as a model of aging. We explore some of the neurobiological mechanisms that appear to be responsible for our aging clock, and consider implications of this work for age-related changes in cognition.     

Modeling melanopsin-mediated effects of light on circadian phase,melatonin suppression,and subjective sleepiness

A physiologically based model of arousal dynamics is improved to incorporate the effects of the light spectrum on circadian phase resetting, melatonin suppression, and subjective sleepiness. To account for these nonvisual effects of light, melanopic irradiance replaces photopic illuminance that was used previously in the model. The dynamic circadian oscillator is revised according to the melanopic irradiance definition and tested against experimental circadian phase resetting dose-response and phase response data. Melatonin suppression function is recalibrated against melatonin dose-response data for monochromatic and polychromatic light sources. A new light-dependent term is introduced into the homeostatic weight component of subjective sleepiness to represent the direct alerting effect of light; the new term responds to light change in a time-dependent manner and is calibrated against experimental data. The model predictions are compared to a total of 14 experimental studies containing 26 data sets for 14 different spectral light profiles. The revised melanopic model shows on average 1.4 times lower prediction error for circadian phase resetting compared to the photopic-based model, 3.2 times lower error for melatonin suppression, and 2.1 times lower error for subjective sleepiness. Overall, incorporating melanopic irradiance allowed simulation of wavelength-dependent responses to light and could explain the majority of the observations. Moving forward, models of circadian phase resetting and the direct effects of light on alertness and sleep need to use nonvisual photoreception-based measures of light, for example, melanopic irradiance, instead of the traditionally used illuminance based on the visual system.     

Effects of a one-hour light pulse on the timing of the circadian rhythm in melatonin secretion in rams

Abstract: The effects of a 1-hr light pulse on the timing of the circadian rhythm in the blood plasma concentration of melatonin were documented in Soay rams. Groups of 5 to 6 animals were transferred from short days (LD 8: 16) to constant dim red light (DD) for 6 days, and were exposed to a 1-hr light pulse at one of 16 different times throughout 24 hr on day 3. Blood samples were collected hourly for 30 hr before (day 2–3) and after the light pulse (day 5–6), and the plasma concentrations of melatonin were measured by radioimmunoassay. The animals were allocated to experimental groups based on the circadian time (CT) when the light pulse was given using two hourly blocks through the circadian day; the onset of enhanced melatonin secretion (melatonin peak) was designated as CT 12. Under DD there was a clearly defined plasma melatonin rhythm in all animals. The mean duration of the melatonin peak was 13.24 ± 0.16 hr (n = 91) and the mean period between the onset of successive melatonin peaks was 23.55 ± 0.10 hr (n = 21). The effect of the 1-hr light pulse on the time of onset of the melatonin peak varied significantly with the circadian time when the light pulse was given (ANOVA, P= 0.031). Light-induced significant (pre- vs post-pulse onset, Students t-test, P < 0.05) phase delays in the onset of the melatonin peak in the early subjective day at CT 2.5 hrs (mean ø: -1.9 hr), and in the early subjective night at CT 12.5 and 14.5 (mean ø: -2.0 hrs), but not at other times. The light pulse never induced significant phase advances. The effects of the light pulse on the offset of plasma melatonin peak did not vary significantly with the time of the light pulse (ANOVA, P= 0.780), although significant differences in the pre- and post-pulse offset occurred at CT 14.5 and 18.5 (mean ø: -1.5 hr). The differential changes in the onset and the offset of the melatonin peak resulted in changes in the duration of the peak (maximum difference between means: 3.8 hr). The results indicate that entrainment occurs under natural 24 hr LD cycles when light impinges on the early subjective night and induces a net phase delay, thus extending the period of the melatonin rhythm to 24 hr. This causes a close phase relationship between the end of the light period and the onset of the melatonin peak as occurs in sheep under natural cycles. The results are also consistent with a multiple oscillator governing melatonin secretion, and that differential entrainment of the component oscillators by light affects the duration of the melatonin peak.     

Circadian rhythms of dopamine, glutamate and GABA in the striatum and nucleus accumbens of the awake rat: modulation by light

Using microdialysis, we investigated the circadian rhythms of the extracellular concentrations of dopamine, glutamate and gamma-aminobutyric acid (GABA) in the striatum and nucleus accumbens of the awake rat. Wistar rats were maintained in a 12 hr dark:12 hr light (12:12) cycle for 2 wk before the experiment began. The neurotransmitter levels were measured every 30 min for 30 hr in control (maintaining the 12:12 cycle) or in experimental conditions under a 24-h light period (continuous light) or under a 24-h dark interval (continuous dark). The dopamine metabolites, DOPAC and HVA, and the main serotonin metabolite, 5-HIAA, were measured along with arginine and glutamine under all conditions. In 12:12 conditions, a circadian rhythm of dopamine, glutamate and GABA was found in both the striatum and nucleus accumbens. Again under 12:12 conditions, DOPAC, HVA, 5-HIAA, and arginine, but not glutamine, fluctuated in a circadian rhythm. In the striatum under constant light conditions, there was a circadian rhythm of dopamine, glutamate, GABA, DOPAC and HVA, but not 5-HIAA. By contrast, when the rats were kept under continuous dark, dopamine and its metabolites, DOPAC and HVA (but not glutamate and GABA), did not fluctuate in a circadian rhythm. In the nucleus accumbens, under both constant light or dark conditions, no changes were found in the circadian rhythm in any of the neurotransmitters and metabolites studied. These findings show that in the striatum, dopamine but not glutamate and GABA, seem to be influenced by light. In the nucleus accumbens, however, the three neurotransmitters had a circadian rhythm, which was independent of light.