Melatonin Levels In Rats Research Articles

Effects of long-term exposure to light or darkness and return to normal light-dark cycle on serum melatonin levels in rats

Increasing evidence suggests that the presence of
 constant light or darkness have diverse effects on circadian physiology. The
 aim of this study is to explore serum levels of melatonin upon return to a
 normal light-dark cycle (LDC) in rats exposed to constant light (LL) or
 darkness (DD). Results showed the different profiles of melatonin levels after
 exposure to LL or DD. Similarly, the restoration of the LDC (12L:12D) modified
 the endogenous melatonin levels. In the LL group, serum melatonin remained at
 levels similar to control values, and when normal LDC was restored, melatonin
 levels of the rats decreased but without significant difference compared to
 control. In the DD group, serum melatonin increased significantly (22%), and
 upon switching to normal LDC, serum melatonin level was significantly decreased
 compared to constant dark condition. Even 15 days later, a significant 76% drop
 in serum melatonin level was still observed in LDC condition. The results
 suggested that prolonged exposure to LL or DD, especially to DD, had profound
 effects on the serum melatonin. LL has little influence and this result can be
 explained by the potential compensation of extrapineal melatonin generated by
 other tissues and organs.

Effect of Daytime Blue-enriched LED Light on the Nighttime Circadian Melatonin Inhibition of Hepatoma 7288CTC Warburg Effect and Progression.

Liver cancer is the second leading cause of cancer death worldwide. Metabolic pathways within the liver and liver cancers are highly regulated by the central circadian clock in the suprachiasmatic nuclei (SCN). Daily light and dark cycles regulate the SCN-driven pineal production of the circadian anticancer hormone melatonin and temporally coordinate circadian rhythms of metabolism and physiology in mammals. In previous studies, we demonstrated that melatonin suppresses linoleic acid metabolism and the Warburg effect (aerobic glycolysis)in human breast cancer xenografts and that blue-enriched light (465-485 nm) from light-emitting diode lighting at daytime (bLAD) amplifies nighttime circadian melatonin levels in rats by 7-fold over cool white fluorescent (CWF) lighting. Here we tested the hypothesis that daytime exposure of tissue-isolated Morris hepatoma 7288CTC-bearing male rats to bLAD amplifies the nighttime melatonin signal to enhance the inhibition of tumor growth. Compared with rats housed under a 12:12-h light:dark cycle in CWF light, rats in bLAD light evinced a 7-fold higher peak plasma melatonin level at the mid-dark phase; in addition, high melatonin levels were prolonged until 4 h into the light phase. After implantation of tissue-isolated hepatoma 7288CTC xenografts, tumor growth rates were markedly delayed, and tumor cAMP levels, LA metabolism, the Warburg effect, and growth signaling activities were decreased in rats in bLAD compared with CWF daytime lighting. These data show that the increased nighttime circadian melatonin levels due to bLAD exposure decreases hepatoma metabolic, signaling, and proliferative activities beyond what occurs after normal melatonin signaling under CWF light.

Effect of Day and Night Desflurane Anaesthesia on Melatonin Levels in Rats.

The aim of this study is to investigate the effect of day and night administration of desflurane anaesthesia on melatonin levels in rats. Twenty-four 15-day-old rats were included in the study and were divided into four groups. The rats were anaesthetised between 19:00-01:00 (night group) and 07:00-13:00 (day group) with 5.7% desflurane concentration in 6 L min-1 100% oxygen. 6 L min-1 oxygen was administered to the control groups. At the end of 6 h of anaesthesia, blood samples were taken, and rats were sacrificed. Blood samples were centrifuged and melatonin levels from plasma samples were measured with radioimmunoassay. There was a statistically significant difference between the groups (p=0.007). Between group day control and group night control there was a statistically significant difference (p=0.042). Further, there was a significant difference between group day control and night desfluran as well (p=0.024). We could not find any difference between other groups. This study showed that 6 hours of 5.7% desflurane anaesthesia during day and night hours did not significantly change melatonin levels.

Effect of day/night administration of three different inhalational anesthetics on melatonin levels in rats

The nocturnal peak of melatonin can be altered after anesthesia and surgery. We aimed to examine the melatonin levels during the day and night after anesthesia with three commonly used inhalational anesthetics. Forty-eight male Wistar albino rats were randomized into eight groups. Rats were administered anesthesia between 7:00 am and 1:00 pm (day groups) or 7:00 pm and 1:00 am (night groups) for 6 hours. At the end of the anesthesia, blood samples were collected for assessing melatonin levels. Mean values of melatonin levels after 6 hours of anesthesia during daytime were 43.17±12.95 for control, 59.79±27.83 for isoflurane, 50.75±34.28 for sevoflurane and 212.20±49.56 pg/mL for desflurane groups. The night groups’ mean melatonin levels were 136.12±33.20 for control, 139.85±56.29 for isoflurane, 117.48±82.39 for sevoflurane and 128.70±44.63 pg/mL for desflurane groups. Desflurane anesthesia between 7:00 am and 1:00 pm significantly increased melatonin levels (p<0.001). Sevoflurane and desflurane anesthesia between 7:00 pm and 1:00 am decreased the melatonin levels but there were no significant differences (p=0.904 and p>0.99, respectively). Isoflurane anesthesia did not significantly change melatonin levels during day or night (p=0.718 and p>0.99, respectively). Our results demonstrate that during daytime desflurane anesthesia can alter melatonin levels. Altered melatonin rhythm following inhalational anesthesia can be related to sleep disorders observed after anesthesia.

The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase

Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. AANAT, which is expressed in the pineal gland, retina, and various other tissues, catalyzes the conversion of serotonin to N-acetylserotonin and is the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AANAT can be used to treat patients with circadian rhythm disorders that are associated with specific circadian rhythm alterations, such as shift work disorder. In the present study, we screened modulators of AANAT activity from the water extracts of medicinal plants. Among the 267 tested medicinal plant extracts, Myricae Cortex (Myrica rubra), Perillae Herba (Perilla sikokiana), and Eriobotryae Folium (Eriobotrya japonica) showed potent inhibition of AANAT activity. Myricetin (5,7,3′,4′,5′-pentahydroxyflavonol), a main component of the Myricae Cortex, strongly inhibited the activity of AANAT and probably block the access to the substrate by docking to the catalytic residues that are important for AANAT activity. Myricetin significantly decreased the nocturnal serum melatonin levels in rats. In addition, the locomotor activity of rats treated with myricetin decreased during the nighttime and slightly increased throughout the day. These results suggest that myricetin could be used as a therapy to increase nighttime alertness by changing the circadian rhythm of serum melatonin and locomotor activity.

Maternal stress induces adult reduced REM sleep and melatonin level

We have previously reported that neonatal maternal deprivation (MD) resulted in a decrease of total sleep and an increase of orexin A in adult rats. Now, we characterized features of sleep, activity, and melatonin levels in rats neonatally treated with MD and control (MC) procedures. Adult male Sprague-Dawley rats were treated with either MD or MC procedures for 10 days starting at postnatal day 4. At 3 months of age, sleep was recorded for 48 h in one set of MD and MC rats, while another set of MD and MC rats was measured for locomotor activity (under LD = 12:12). Melatonin levels in the blood, pineal gland, and hypothalamus were measured as well as clock protein level in the hypothalamus. Compared to the MC rats, REM sleep in the MD rats was significantly reduced in the light periods but not in the dark periods. Both quiet wake and total wake in the MD rats were significantly increased during the light period compared to the MC rats. The weight of the pineal gland of the MD rats was significantly smaller than in MC rats. Melatonin levels of the MD group were significantly reduced in the pineal gland and hypothalamus compared to the MC group. No significant difference was identified between groups in the expression of the clock protein in the hypothalamus. Neonatal MD resulted in reduced REM sleep and melatonin levels, without changes of circadian cycle of locomotor activity and levels of clock protein.

The effect of acute swimming exercise on plasma melatonin levels in rats

This study aims to determine the changes in plasma melatonin levels of rats performing acute swimming exercise, immediately following the exercise and after 24 and 48 hours. The study included 40 Spraque Dawley species adult male rats divided in to 4 groups as follows: group 1: general control group, group 2: swimming group A, the animals were decapitated after performing 30-minute acute swimming exercise, group 3: Swimming group B, the animals were decapitated 24 hours after performing 30-minute acute swimming exercise and group 4: swimming group C, the animals were decapitated 48 hours after performing 30-minute acute swimming exercise. Blood samples were collected from all experimental animals by decapitation method and plasma melatonin levels were determined according to RIA method. The comparison of plasma melatonin levels among groups revealed that group 3 had the highest plasma melatonin levels (p<0.01). The levels in group 1 (control) and group 4 were not different. The lowest plasma melatonin levels were found in group 2 (p<0.01). The results of our study demonstrate that plasma melatonin levels that decrease immediately after acute swimming exercise increase significantly after 24 hours and restore to resting levels after 48 hours (Tab. 1, Ref. 15).

411 POSTER Spleen tyrosine kinase as a novel candidate metastasis suppressor for human oral squamous cell carcinoma

Two-month-old outbred female LIO rats were injected weekly with a single dose of 1,2-dimethylhydrazine (DMH; 21 mg/kg of body weight) administered s.c. for 15 consecutive weeks. From the day of the 1st injection of the carcinogen the part of rats were given five days a week during the night time (from 18.00 h to 08.00 h) melatonin dissolved in tap water, 20 mg/l. The experiment was terminated in 6 months after the first injection of the carcinogen. The concentration of melatonin in the serum was estimated by radioimmunoassay in rats exposed to DMH alone or in intact control rats in the morning (between 10.00 and 11.00 hours) and night (between 24.00 and 01.00 hours) time. Number of melatonin-containing cells (M-cells) and their optical density were estimated by immunohistology in normal mucosa of glandular stomach, duodenum, ileum and descending colon of tumor-bearing animals from groups exposed to DMH or DMH+melatonin. It was shown that serum melatonin levels in rats with colon tumors was increased as compared with controls. However there was no diurnal rhythm of serum melatonin of colon tumor-bearing animals as compared to intact controls. The number of M-cells was decreased in all tissues studied in rats with DMH-induced colon tumors in comparison to corresponding controls: by 2.0 times in stomach, by 1.8 time in duodenum, by 1.3 times in ileum, and by 1.8 times in colon. In ileum and colon of rats treated with DMH+melatonin the number of M-cells was similar to control level whereas in stomach and duodenum this number was significantly higher than that in rats treated with DMH alone, but less than in corresponding controls. Relative content of melatonin in enterochromaffin cells of all parts of gastrointestinal tract evaluated as optical density of the cells and was decreased in rats exposed with DMH alone in comparison to the controls and was normalized and similar to the norm level in rats treated with DMH+melatonin. Thus, exogenous melatonin prevent a decrease in numbers of melatonin-containing cells as was observed in gastrointestinal tract (GIT) of rats exposed to DMH. This preventive action of melatonin correlated well with its anticarcinogenic effect.

No effects of 900 MHz and 1800 MHz electromagnetic field emitted from cellular phone on nocturnal serum melatonin levels in rats

In this study, the effects of exposure to a 900 MHz and 1800 MHz electromagnetic field (EMF) on serum nocturnal melatonin levels of adult male Sprague-Dawley rats were studied. Thirty rats were used in three independent groups, 10 of which were exposed to 900 MHz, 10 of which were exposed to 1800 MHz and 10 of which were sham-exposed (control). The exposures were performed 30 min/day, for five days/week for four weeks to 900 MHz or 1800 MHz EMF Control animals were kept under the same environmental conditions as the study groups except with no EMF exposure. The concentration of nocturnal melatonin in the rat serum was measured by using a radioimmunoassay method. There were no statistically significant differences in serum melatonin concentrations between the 900 MHz EMF group and the sham-exposed group (P > 0.05). The values at 12:00 pm were 39.11 +/- 6.5 pg/mL in the sham-exposed group and 34.97 +/- 5.1 pg/mL in the 900 MHz EMF-exposed group. Also, there were no statistically significant differences in serum melatonin concentrations between the sham-exposed group and the 1800 MHz EMF-exposed group (P > 0.05). The values at 12:00 pm were 39.11 +/- 6.5 pg/mL in the sham-exposed group and 37.96 +/- 7.4 pg/mL in the exposed group. These results indicate that mobile phones, emitting 900 and 1800 MHz EMF, have no effect on nocturnal serum melatonin levels in rats.

Both zinc deficiency and supplementation affect plasma melatonin levels in rats.

At physiological levels, zinc and various hormones affect each other reciprocally. Reduction in zinc levels in pinealectomized rats suggests the relation between zinc and melatonin. The effect of both zinc deficiency and supplementation on plasma melatonin levels in rats were investigated in this study. The study was done in Selçuk University, Experimental Medicine Research and Application Center. Twenty-four adult male Sprague Dawley rats were divided into 3 groups. Eight rats were fed with zinc-deficient diet. Zinc supplementation was administered intaperitoneally to 8 rats. The remaining 8 rats were used as controls. All rats sacrificed 3 weeks later. Plasma melatonin and zinc levels were determined. The plasma zinc levels of the zinc-supplemented group were higher than those of the other groups as expected (P<0.01). Similarly, the melatonin levels in the zinc-supplemented group were higher than those in the other groups. A significant decrease was observed in melatonin levels of the zinc-deficient group compared to the control and zinc-supplemented group (P<0.01). The results of this study suggest that zinc deficiency decreases the melatonin levels and zinc supplementation may increase the plasma melatonin levels in rats.

Evidence against alpha2-adrenoceptor involvement in the regulation of rat melatonin synthesis by ambient lighting

This study was carried out to clarify the role of α 2-adrenoceptors in the regulation of pineal melatonin synthesis. Medetomidine, a selective α 2-adrenoceptor agonist, was previously found to be a potent suppressor of nocturnal melatonin levels in rats. Medetomidine and α 2-adrenoceptor antagonists atipamezole and yohimbine were injected into rats in different conditions, and their pineal melatonin contents were measured by radioimmunoassay. Experiment 1: Blocking the α 2-adrenoceptors and possible non-adrenergic binding sites with atipamezole did not counteract the light-induced suppression of nocturnal melatonin. These receptors are, thus, not essential for the suppression of melatonin by light. Experiment 2: Blocking the α 2-adrenoceptors with atipamezole or yohimbine did not sensitize the pineal melatonin synthesis to daytime darkness in the light/dark-entrained rats. The binding sites are not involved in keeping the daytime melatonin levels low, even in darkness. Experiment 3: The rats were sensitized to daytime darkness by keeping them for seven days in constant light. The dark-elicited melatonin rise was suppressed by a lower dose of medetomidine than the normal nocturnal rise in light/dark-entrained rats, while atipamezole had no effect. The results showed that α 2-adrenoceptor insufficiency is not involved in the constant light-induced pineal supersensitivity. In summary, the experiments indicated that the physiological regulation of melatonin synthesis by ambient lighting in rats does not depend on α 2-adrenergic mechanisms.

Melatonin and colon carcinogenesis: II. Intestinal melatonin-containing cells and serum melatonin level in rats with 1,2-dimethylhydrazine-induced colon tumors

Two-month-old outbred female LIO rats were injected weekly with a single dose of 1,2-dimethylhydrazine (DMH; 21 mg/kg of body weight) administered s.c. for 15 consecutive weeks. From the day of the 1st injection of the carcinogen the part of rats were given five days a week during the night time (from 18.00 h to 08.00 h) melatonin dissolved in tap water, 20 mg/l. The experiment was terminated in 6 months after the first injection of the carcinogen. The concentration of melatonin in the serum was estimated by radioimmunoassay in rats exposed to DMH alone or in intact control rats in the morning (between 10.00 and 11.00 hours) and night (between 24.00 and 01.00 hours) time. Number of melatonin-containing cells (M-cells) and their optical density were estimated by immunohistology in normal mucosa of glandular stomach, duodenum, ileum and descending colon of tumor-bearing animals from groups exposed to DMH or DMH+melatonin. It was shown that serum melatonin levels in rats with colon tumors was increased as compared with controls. However there was no diurnal rhythm of serum melatonin of colon tumor-bearing animals as compared to intact controls. The number of M-cells was decreased in all tissues studied in rats with DMH-induced colon tumors in comparison to corresponding controls: by 2.0 times in stomach, by 1.8 time in duodenum, by 1.3 times in ileum, and by 1.8 times in colon. In ileum and colon of rats treated with DMH+melatonin the number of M-cells was similar to control level whereas in stomach and duodenum this number was significantly higher than that in rats treated with DMH alone, but less than in corresponding controls. Relative content of melatonin in enterochromaffin cells of all parts of gastrointestinal tract evaluated as optical density of the cells and was decreased in rats exposed with DMH alone in comparison to the controls and was normalized and similar to the norm level in rats treated with DMH+melatonin. Thus, exogenous melatonin prevent a decrease in numbers of melatonin-containing cells as was observed in gastrointestinal tract (GIT) of rats exposed to DMH. This preventive action of melatonin correlated well with its anticarcinogenic effect.

Effect of continuous melatonin infusions on steady-state plasma melatonin levels in rats under near physiological conditions.

It was the aim of this study to measure the actual amount of melatonin required for elevating the circulating hormone from low daytime levels to the 10-fold higher nocturnal steady-state concentrations in rats. For this purpose, escalating doses of melatonin were continuously infused into the right jugular vein and blood samples were repeatedly drawn from the left jugular vein for a period of 2 hr in freely moving catheterized rats. In order to achieve an about 10-fold elevation of the plasma melatonin concentration, 500 ng melatonin/hr had to be infused, i.e., about 300 times the normal nocturnal melatonin content of the pineal. Infusions of up to 61 ng melatonin/hr (equivalent to the melatonin content of 40 pineals at darkness) failed to cause a significant rise of the low daytime steady-state concentrations in the blood. If the dose of 500 ng melatonin/h was infused at night, a less-pronounced rise of the blood levels was observed, as compared to that caused by the infusion of the same dose during daytime. No differences were found in the rate of metabolism between daytime and nighttime. The results of this study indicate 1) that the low basal concentrations of melatonin in the blood are not affected by an increased melatonin supply up to a certain critical threshold, 2) that the rat pineal gland would have to release all its melatonin content almost every 10 sec in order to sustain the elevated steady-state level of melatonin in the circulation during the dark period, and 3) that significant day/night differences exist in the disposition of circulating melatonin if administered in near physiological amounts and under near physiological conditions.

Inconsistent suppression of nocturnal pineal melatonin synthesis and serum melatonin levels in rats exposed to pulsed DC magnetic fields.

The purpose of these experiments was to determine whether the exposure of rats at night to pulsed DC magnetic fields (MF) would influence the nocturnal production and secretion of melatonin, as indicated by pineal N-acetyltransferase (NAT) activity (the rate limiting enzyme in melatonin production) and pineal and serum melatonin levels. By using a computer-driven exposure system, 15 experiments were conducted. MF exposure onset was always during the night, with the duration of exposure varying from 15 to 120 min. A variety of field strengths, ranging from 50 to 500 microT (0.5 to 5.0 G) were used with the bulk of the studies being conducted using a 100 microT (1.0 G) field. During the interval of DC MF exposure, the field was turned on and off at 1-s intervals with a rise/fall time constant of 5 ms. Because the studies were performed during the night, all procedures were carried out under weak red light (intensity of <5 microW/cm2). At the conclusion of each study, a blood sample and the pineal gland were collected for analysis of serum melatonin titers and pineal NAT and melatonin levels. The outcome of individual studies varied. Of the 23 cases in which pineal NAT activity, pineal melatonin, and serum melatonin levels were measured, the following results were obtained; in 5 cases (21.7%) pineal NAT activity was depressed, in 2 cases (8.7%) studies pineal melatonin levels were lowered, and in 10 cases (43.5%) serum melatonin concentrations were reduced. Never was there a measured rise in any of the end points that were considered in this study. The magnitudes of the reductions were not correlated with field strength (i.e., no dose-response relationships were apparent), and likewise the reductions could not be correlated with the season of the year (experiments conducted at 12-month intervals under identical exposure conditions yielded different results). Duration of exposure also seemed not to be a factor in the degree of melatonin suppression. The inconsistency of the results does not permit the conclusion that pineal melatonin production or release are routinely influenced by pulsed DC MF exposure. In the current series of studies, a suppression of serum melatonin sometimes occurred in the absence of any apparent change in the synthesis of this indoleamine within the pineal gland (no alteration in either pineal NAT activity or pineal melatonin levels). Because melatonin is a direct free radical scavenger, the drop in serum melatonin could theoretically be explained by an increased uptake of melatonin by tissues that were experiencing augmented levels of free radicals as a consequence of MF exposure. This hypothetical possibly requires additional experimental documentation.

Mechanism by which 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) reduces circulating melatonin levels in the rat

We have previously shown that the prototype for halogenated aromatic hydrocarbons, 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), diminishes serum melatonin concentration at the same dose in both the most TCDD-susceptible (Long-Evans, Turku AB; L-E) and the most TCDD-resistant (Han/Wistar, Kuopio; H/W) rat strain. The change developed within 24 h and persisted for at least 28 days after TCDD exposure; was independent of the time of day and was not associated with any morphological damage to the pineal gland. In the present study, we investigated the mechanism of this endocrine effect. Despite a 40–50% decrease in circulating melatonin levels, the pineal content of melatonin, serotonin and 5-hydroxyindole acetic acid remained unaltered and the rate-limiting enzyme of pineal melatonin biosynthesis, N-acetyltransferase, displayed only a relatively minor suppression in activity (30%) in TCDD-treated L-E rats. Likewise, TCDD did not influence the ability of pineal glands from L-E rats to synthesize and secrete melatonin in ex vivo or in vitro experiments. TCDD accelerated the disappearance of exogeneous melatonin from the serum in both rat strains. This enhancement probably did not originate in the liver, because liver perfusion studies revealed that even control rat livers were capable of total melatonin clearance in spite of the fact that the melatonin concentration far exceeded physiological levels. Urine excretion of the normal main metabolite of melatonin, 6-hydroxymelatoninsulfate, was reduced by TCDD treatment in both strains. This was accompanied by an altered HPLC pattern of metabolites, especially in H/W rats. We conclude that TCDD decreases serum melatonin levels in rats by enhancing the peripheral, evidently extrahepatic, metabolism of the hormone.

Decreased Serum Melatonin Levels in Rats with Experimental Autoimmune Uveitis/Pinealitis and in Patients with Uveitis

The authors measured serum levels of the pineal hormone melatonin to investigate the possibility of pineal dysfunction in both rats with experimental autoimmune uveitis/pinealitis (EAU/EAP) and uveitis patients. The serum melatonin concentrations of EAU/EAP rats were measured by radioimmunoassay over a 24-hour (h) period, and in uveitis patients at night (0200 h). Melatonin concentrations were assayed in six patients with Behçet's disease, four with Vogt-Koyanagi-Harada (VKH) disease, three with sarcoidosis, three with Kirisawa-type uveitis, and one with tubulointerstitial nephritis and uveitis syndrome. Nocturnal serum melatonin levels were significantly lower in Lewis rats with EAU/EAP (2200 h: 33.6±20.4 pg/ml, 0200 h: 43.2±13.9 pg/ml) than in the controls (2200 h: 117.5±25.3 pg/ml, 0200 h: 132.4±20.2 pg/ml) (p>0.01, at 2200 h and 0200 h). Melatonin levels were significantly lower in VKH disease (20.7±10.5 pg/ml) (p>0.01) and Behçet's disease (42.1±42.5 pg/ml) (p>0.05) than in the controls (79.4±36.7 pg/ml). These results suggest that there is a decrease in pineal gland function due to pinealitis in EAU/EAP rats. The markedly decreased nocturnal serum melatonin levels may also be related to the presence of retinal uveitogenic antigens in uveitis patients.

Effect of MR imaging on the normal human pineal body: measurement of plasma melatonin levels.

Production of melatonin, a hormone synthesized and secreted by the pineal body, has been suppressed by electromagnetic fields in some but not all animal studies. Magnetic resonance (MR) imaging at 1.5 T was evaluated for its ability to modulate the level of melatonin in eight male volunteers. Subjects were exposed to three conditions, respectively, between 1:00 and 2:00 AM on different nights: (a) a series of routine MR pulse sequences for brain imaging in dark conditions, (b) dark control conditions, and (c) bright-light control conditions. Plasma was analyzed for melatonin and cortisol levels. Hormonal changes were analyzed by one-factor repeated measures within-subject analysis of variance. These conditions were associated with significant differences in melatonin levels: F(2, 6) = 7.95, and P = .021. Subjects exposed to darkness showed a typical increase in melatonin concentration. Subjects exposed to bright light showed a characteristic suppression of melatonin concentration. Those exposed to the MR imaging fields showed an increase in melatonin level similar to that seen in the dark control condition. Light and MR imaging had no significant effects on cortisol levels. Thus, MR imaging at field strengths known to modulate melatonin levels in rats did not suppress melatonin production in human subjects.

Effects of indirectly acting 5-HT receptor agonists on circulating melatonin levels in rats

Because circulating melatonin levels are generally thought to be under the strict control of pineal N-acetyltransferase, little attention has been paid to the impact of an altered availability of serotonin (5-HT) on melatonin formation. In order to see whether melatonin synthesis is stimulated by an increased availability of free, cytosolic 5-HT, we studied the effects of 5-HT precursors, 5-HT releasers and reuptake inhibitors and of monoamine oxidase inhibitors, alone and in combination, on circulating melatonin levels in experimental animals. The administration of tryptophan and 5-HT-releasing drugs (fenfluramine, ±3,4-methylenedioxymethamphetamine) to rats caused a dose- and time-dependent elevation of circulating melatonin levels during the day and night. This increase in melatonin was further enhanced by inhibition of monoamine oxidase. The elevation of plasma melatonin caused by 5-HT-releasing drugs was prevented by prior administration of fluoxetine. Monoamine oxidase inhibitors and fluoxetine alone had no effect on circulating melatonin levels. These findings indicate that the administration of indirectly acting 5-HT receptor agonists which increase the free cytoplasmic pool of 5-HT may also elevate circulating melatonin levels. The results of this study suggest that the rate of pineal melatonin synthesis is dependent on the free cytoplasmic pool of 5-HT in pinealocytes and that the drug-induced elevation of this pool stimulates melatonin formation and increases circulating melatonin levels. At least some of the effects of indirectly acting 5-HT receptor agonists, e.g. on sleep, mood, food intake, pain perception, and neuroendocrine secretion, may therefore be mediated by the elevation of circulating melatonin and the subsequent activation of central melatonin receptors.

Reduction in pineal N-acetyltransferase activity and pineal and serum melatonin levels in rats after their exposure to red light at night

Pineal gland N-acetyltransferase (NAT) activity and pineal and serum levels of melatonin declined linearly in albino rats exposed to different irradiances (low, 170 μW/cm 2; moderate, 420 μW/cm 2; high, 1040 μW/cm 2) red light during the middle of the night. High intensity red light (1040 μW/cm 2) was as effective as white light (670 μW/cm 2) in suppressing pineal NAT activity and pineal and serum melatonin levels. The lowered melatonin levels and the reduction in NAT activity following exposure to red light suggest that red light cannot be regarded as ‘safe’ light when studying circadian melatonin production in the albino rat, at least at the intensities used in this experiment.

Effects of exposure to a circularly polarized 50-Hz magnetic field on plasma and pineal melatonin levels in rats.

We sought to determine whether a 6-week exposure to a 50-Hz rotating magnetic field influences melatonin synthesis by 11-18 week-old Wistar-King male rats. Rats were exposed continuously to a rotating magnetic field at 1, 5, 50, or 250 microT (spatial vector rms) for 6 weeks, except for twice-weekly breaks of about 2 h for cleaning of cages and feeding. The rats were housed in exposure and sham-exposure facilities, which were located in the same room, under a 12:12 light-dark photoperiod (lights on at 06:00 h). The room was constantly illuminated by 4 small, dim red lights (< 0.07 lux in dark period). Levels of plasma and pineal gland melatonin were determined by radioimmunoassay. A significant decrease of melatonin was observed between the control group and groups exposed to a magnetic field at a flux density in excess of 1 microT during the night time, but no statistical differences were found among the exposed groups. These results indicate that subchronic exposure of albino rats to a 50-Hz rotating magnetic field influences melatonin production and secretion by the pineal gland.