Interindividual differences in the pattern of melatonin secretion of the Wistar rat (original) (raw)
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The Daily Melatonin Pattern in Djungarian Hamsters Depends on the Circadian Phenotype
Chronobiology International, 2011
Djungarian hamsters (Phodopus sungorus) bred at the Institute of Halle reveal three different circadian phenotypes. The wild type (WT) shows normal locomotor activity patterns, whereas in hamsters of the DAO (delayed activity onset) type, the activity onset is continuously delayed. Since the activity offset in those hamsters remains coupled to "light-on," the activity time becomes compressed. Hamsters of the AR (arrhythmic) type are episodically active throughout the 24 h. Previous studies showed that a disturbed interaction of the circadian system with the light-dark (LD) cycle contributes to the phenomenon observed in DAO hamsters. To gain better insight into the underlying mechanisms, the authors investigated the daily melatonin rhythm, as it is a reliable marker of the circadian clock. Hamsters were kept individually under standardized laboratory conditions (LD 14:10, T = 22°C ± 2°C, food and water ad libitum). WT, DAO (with exactly 5 h delay of activity onset), and AR hamsters were used for pineal melatonin and urinary 6-sulfatoxymelatonin (aMT6s) measurement. Pineal melatonin content was determined at 3 time points: 4 h after "light-off" [D + 4], 1 h before "light-on" [L − 1], and 1 h after "light-on" [L + 1]). The 24-h profile of melatonin secretion was investigated by transferring the animals to metabolic cages for 27 h to collect urine at 3-h intervals for aMT6s analysis. WT hamsters showed high pineal melatonin content during the dark time (D + 4, L − 1), which significantly decreased at the beginning of the light period (L + 1). In contrast, DAO hamsters displayed low melatonin levels during the part of the dark period when animals were still resting (D + 4). At the end of the dark period (L − 1), melatonin content increased significantly and declined again when light was switched on (L + 1). AR hamsters showed low melatonin levels, comparable to daytime values, at all 3 time points. The results were confirmed by aMT6s data. WT hamsters showed a marked circadian pattern of aMT6s excretion. The concentration started to increase 3 h after "light-off" and reached daytime values 5 h after "light-on." In DAO hamsters, in contrast, aMT6s excretion started about 6 h later and reached significantly lower levels compared to WT hamsters. In AR animals, aMT6s excretion was low at all times. The results clearly indicate the rhythm of melatonin secretion in DAO hamsters is delayed in accord with their delayed activity onset, whereas AR hamsters display no melatonin rhythm at all. Since the regulatory pathways for the rhythms of locomotor activity and melatonin synthesis (which are downstream from the suprachiasmatic nucleus [SCN]) are different but obviously convey the same signal, we conclude that the origin of the phenomenon observed in DAO hamsters must be located upstream of the SCN, or in the SCN itself.
Journal of Pineal Research, 2007
Abstract: Melatonin is an essential component for circadian system function, whose daily plasma secretory rhythm is driven by the suprachiasmatic nucleus (SCN), contributing to the communication of temporal messages from the central circadian clock to all cells. Melatonin secretion peaks in the dark, regardless of whether animals are diurnal or nocturnal. To date, the precise mechanisms that explain how the circadian system is configured as nocturnal or diurnal remain unknown. The present study examines mid-day and midnight melatonin plasma levels and the influence of exogenous melatonin on the circadian system phasing of Octodon degus, a diurnal rodent, which exhibits nocturnal and diurnal chronotypes when free access to a wheel is provided. Plasma levels of melatonin were determined by RIA in blood samples taken from the jugular vein at mid-light (ML) and mid-dark (MD). Melatonin (0.5 mg/kg b.wt.) was orally administered in their drinking water for 30 days, 2 hr before the onset of darkness. The results showed that plasma melatonin levels and their qualitative effects, hypothermia and improved synchronization with no modification in the 24-hr wheel running activity (WR), were similar in both nocturnal and diurnal degus. Furthermore, melatonin can be used to improve the impaired circadian rhythmicity observed in aged animals, with no rebound effect after ceasing the treatment. It is concluded that plasma melatonin levels and the differential responses to melatonin do not seem to be responsible for nocturnal and diurnal chronotypes, and thus other mechanisms upstream, within, or downstream from the SCN should be investigated.
The effect of exogenous melatonin (MEL) on the circadian system in nocturnal species has been extensively studied, but little is known about its chronobiotic effect in diurnal mammals. The present study investigated the effect of exogenous MEL on the circadian locomotor activity rhythm in the diurnal rodent Ar6icanthis ansorgei. Male animals (n= 34) were fitted with a subcutaneous catheter for daily infusion of MEL (1 h; 100 mg) and their running wheel activity was recorded. The results showed that administration of MEL to animals free-running in DD entrained their activity rhythm by phase advances at circadian time (CT) 10.62, and by phase delays at CT −0.40 (CT 0, activity onset). The range of entrainment was 17 and 11.5 min for advance and delay stimuli, respectively. Interestingly, in the nocturnal rat and the A. ansorgei, entrainment of the activity rhythm to exogenous MEL by phase advances occurs at exactly the same phase of the circadian cycle. In both nocturnal and diurnal species, the sensitivity window for exogenous MEL is located near the activity/rest transition points. It is concluded that the functional properties of entrainment to exogenous MEL are similar to those of other nonphotic stimuli. Furthermore, A. ansorgei might be an interesting animal model for studies on the chronobiotic effects of exogenous MEL in diurnal mammals including humans.
Melatonin-induced phase and dose responses in a diurnal mammal, Funambulus pennantii
Chronobiology International, 2020
Melatonin, an essential pineal hormone, acts as a marker of the circadian clock that regulates biological rhythms in animals. The effects of exogenous melatonin on the circadian system of nocturnal rodents have been extensively studied; however, there is a paucity of studies on the phase-resetting characteristics of melatonin in diurnal rodents. We studied the phase shifting effects of exogenous melatonin as a single melatonin injection (1 mg/kg) at various phases of the circadian cycle on the circadian locomotor activity rhythm in the palm squirrel, Funambulus pennantii. A phase response curve (PRC) was constructed. Adult male squirrels (N = 10) were entrained to a 12:12 h light-dark cycle (LD) in a climate-controlled chronocubicle with food and water provided ad libitum. After stable entrainment, squirrels were transferred to constant dark condition (DD) for free-running. Following stable free run, animals were administered a single dose of melatonin (1 mg/kg in 2% ethanol-phosphate buffered saline (PBS) solution) or vehicle (2% ethanol-PBS solution) at circadian times (CTs) 3 h apart to evoke phase shifts. The phase shifts elicited at various CTs were plotted to generate the PRC. A dose response curve was generated using four doses (0.5, 1, 2 and 4 mg/kg) administered at the CT of maximum phase advance. Melatonin evoked maximum phase advances at CT0 (1.23 ± 0.28 h) and maximum phase delays at CT15 (0.31 ± 0.09 h). In the dose response experiment, maximal phase shifts were evoked with 1 mg/kg. In contrast, no significant shifts were observed in control groups. Our study demonstrates that the precise timing and appropriate dose of melatonin administration is essential to maximize the amelioration of circadian rhythm-related disorders in a diurnal model.
General and Comparative Endocrinology, 1997
Nocturnal patterns of pineal melatonin concentrations were measured at hourly intervals in the European hamster, Cricetus cricetus, maintained under different natural or experimental environmental conditions. There were pronounced variations in the night peak of pineal melatonin both in the duration and the amplitude of the melatonin peak and in the onset and decline of melatonin synthesis. The duration of the melatonin peak increased proportionnally with increased dark period. The amplitude increased abruptly from LD 16/8 to LD 15/9 and remained constant in all other photoperiods. The onset of synthesis started 6:00 hours after the onset of darkness in LD 16/8, 15/9, and 14/10, while it started 4:00 hours after dark onset in shorter photoperiods (LD 12/12 and 10/14). This result is opposite to that observed in the rat. The decline of synthesis was delayed as darkness increased and was directly related to lights on in long photoperiods, while it was endogenous in short photoperiods. Temperature, under a long photoperiod, also seems to be implicated in the regulation of the amplitude of the melatonin peak. r 1997 Academic Press
Behavioural Brain Research, 2002
The effect of exogenous melatonin (MEL) on the circadian system in nocturnal species has been extensively studied, but little is known about its chronobiotic effect in diurnal mammals. The present study investigated the effect of exogenous MEL on the circadian locomotor activity rhythm in the diurnal rodent Ar6icanthis ansorgei. Male animals (n= 34) were fitted with a subcutaneous catheter for daily infusion of MEL (1 h; 100 mg) and their running wheel activity was recorded. The results showed that administration of MEL to animals free-running in DD entrained their activity rhythm by phase advances at circadian time (CT) 10.62, and by phase delays at CT −0.40 (CT 0, activity onset). The range of entrainment was 17 and 11.5 min for advance and delay stimuli, respectively. Interestingly, in the nocturnal rat and the A. ansorgei, entrainment of the activity rhythm to exogenous MEL by phase advances occurs at exactly the same phase of the circadian cycle. In both nocturnal and diurnal species, the sensitivity window for exogenous MEL is located near the activity/rest transition points. It is concluded that the functional properties of entrainment to exogenous MEL are similar to those of other nonphotic stimuli. Furthermore, A. ansorgei might be an interesting animal model for studies on the chronobiotic effects of exogenous MEL in diurnal mammals including humans.
Journal of Neuroendocrinology, 1995
The pineal gland, via the daily pattern of melatonin (MEL) secretion, is directly involved in the conduction of photoperiodic information. The duration of MEL secretion is proportional to the duration of the dark period and, whatever the photoperiod is, MEL synthesis occurs 3 or 4 h after the dark onset in Syrian hamsters. In order to determine the relative importance of the duration or the coincidence hypothesis, a daily infusion protocol was used in sexually active pinealectomized hamsters. Long duration of MEL infusion (10 h) completely inhibit testes whereas short duration infusion (5 h) had no effect. When the animals were infused twice within 2 h 30 min separated by 3 h, they presented a complete gonadal atrophy, similar to the one observed with the 10 h infusion. Measurement of plasma MEL during the infusion and seperation periods revealed that MEL reached physiological nighttime values during the infusion period and fell to daytime values 1 h after the end of an infusion period. Thus, the results could not be due to a time additive action of the two MEL pulses. An intermediate response was observed when the 2 signals were applied across the Iightldark transition. Gonadal regression did not occur
Steroids, 1991
The major junction of the mammul~arl pineal gland appears to be its central role in ~~~otoperio~iism. The pineal hormone, me~atonin, is synt~tesi~ed and secreted primuri~y ut nig~~t, lander the control of a circadian oscillator that is entrained to the light-dark cycle. Both the circadian phase and the duration of the nocturnal peak of meiatonin secretion are established primarily by interactions between the endogenous circadian oscillator and the daily photic cycle. The duration of the melatonin peuk varies inversely with day length, and this relationship between day length and the durution of each circadian melatonin peak appears to be an integral part of the photoperiodic mechanism. When pinealectomized ani~nals are given daily rne~at[~nin infusions of long dt~ratioi~, they exhibit physiologic. re.~pon~~es that normally are observed during exposure to short day ph~~t~~period~~; when administered sh~~rt-duration melatonin infusions, the animals display longphotoperiod-type responses. In addition to the importance of the duration of each melatonin peak, certain other parameters appear to be sign$cant. If a longduration infusion of melatonin is interrupted by a period of 2 hours or more without melatonin (i.e., to produce two short duration infusions), the responses are those typical for long day-exposed animals. Thus, to elicit short day-type responses, each l~~ng-~~arat~on melatt)nin peak must be rel~~tiv~~iy continuous; responses are not determined simply by the total time of exposure to melatonin in euch ~ir~ad~a~~ cycle. Also, long-duration melatonin peaks may nor be effective to elicit photoperiod-type responses unless they are present at frequencies of nearly once every 24 hours or more.
Comparative effects of a melatonin agonist on the circadian system in mice and Syrian hamsters
Brain Research, 1997
S-20098 has potent and specific agonist properties on melatonin receptors both in vitro and in vivo. Behavioral studies on rodents already showed that repeated intraperitoneal administration of S-20098 could dose-dependently alter the functioning of the circadian clock. To determine whether single administration of S-20098 could alter the circadian rhythms of rodents, we first used the Ž . Ž . phase-response curve PRC approach in two different species: Syrian hamsters and mice C3HrHeJ . Our results show that the shape, circadian times and extent of the PRC to S-20098 look very similar in mice and hamsters. In both species, the phase advance portion of the PRC to S-20098 is limited to a 3 h window preceding the onset of locomotor activity, but the magnitude of phase shifts is larger in mice. We also tested the phase shifting effects of increasing doses of S-20098 during the interval of maximal sensitivity to this compound. Treatment with S-20098 induces dose-dependent phase shifts, with maximal shifts observed after injections of 20 and 25 mgrkg S-20098 i.p., respectively, in mice and hamsters. Those results are in agreement with the limited distribution of melatonin-binding sites within the circadian clock of adult Syrian hamsters, as compared to other rodents. q 1997 Elsevier Science B.V.