Melatonin attenuates photic disruption of circadian rhythms in Siberian hamsters

1997 ◽  
Vol 273 (4) ◽  
pp. R1540-R1549 ◽  
Author(s):  
Norman F. Ruby ◽  
Tom Kang ◽  
H. Craig Heller

Body temperature (Tb) was recorded via a biotelemetry system from 28 adult male Siberian hamsters maintained in a light-dark (LD) cycle of 16 h light/day for several months. After Tb was recorded for 3 wk, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8 LD cycle for the remainder of the experiment. Hamsters were injected daily with melatonin or vehicle solution for several weeks, beginning either 2 mo after ( experiment 1) or on the day of ( experiment 2) the phase shift; injections occurred within 30 min of dark onset. In experiment 1, 75% of animals free ran with circadian periods >24 h, beginning on the day of the phase shift, and never reentrained to the LD cycle; no hamsters unambiguously entrained to daily injections. In contrast, 78% of animals in experiment 2 entrained to melatonin injections, and 71% of those animals subsequently reentrained to the photocycle when the injection regimen ended. No vehicle-treated animals entrained to the injection schedule. Melatonin had no effect on daily mean Tb and Tb rhythm amplitude in either experiment; however, melatonin doubled the duration of a hyperthermic response that occurred after each injection. Thus melatonin can prevent loss of entrainment induced by a phase shift of the LD cycle but cannot restore entrainment to free-running animals. Failure to reentrain in the presence of two appropriately coordinated entraining agents also suggests that a phase shift of the photocycle can diminish the sensitivity of the circadian system to both photic and nonphotic input.

1979 ◽  
Vol 34 (5-6) ◽  
pp. 470-473 ◽  
Author(s):  
A. Johnsson ◽  
W. Engelmann ◽  
W. Klemke ◽  
Aud Tveito Ekse

Abstract The body temperature, activity-rest time, electrolytes of urine samples and mood was measured in two persons during a 19 day period under continuous light conditions in the arctic (vicinity of Ny Ålesund, Svalbard-Spitsbergen). For temperature recording a new thermoprobe and a portable printer was used. Possible week Zeitgeber of the 24 hour day did not synchronize the circadian system, since circadian rhythms of about 26 hours were found. These results open up the pos­ sibility to study effects of drugs on the circadian system of humans under Svalbard conditions.


1996 ◽  
Vol 271 (4) ◽  
pp. R881-R890 ◽  
Author(s):  
N. F. Ruby ◽  
A. Saran ◽  
T. Kang ◽  
P. Franken ◽  
H. C. Heller

Body temperature (Tb) and locomotor activity were recorded telemetrically from male Siberian hamsters (Phodopus sungorus sungorus) that were 3 or 12 mo of age and maintained in a light-dark (LD) cycle of 16 h light/day for 2-4 mo. After 3 wk of Tb recording, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8-h LD cycle for the remainder of the experiment. Tb and activity rhythms of all animals were stably entrained to the LD cycle before the phase shift. After the phase shift, > or = 80% of the animals in each age group failed to reentrain and expressed free-running Tb rhythms with stable periods that ranged from 24.33 to 26.33 h; one hamster in each age group reentrained within several days. Tb became arrhythmic in 10% of all animals immediately after, and in 28% of free running animals several weeks after, the phase shift. Changes in tau and phase of activity rhythms closely paralleled Tb rhythms in individual hamsters. Daily mean Tb was unchanged, but Tb rhythm amplitude decreased by 25-50% in individual animals after the phase shift. We believe this to be the first report of neurologically intact animals failing to reentrain to a phase shift of the LD cycle. These phenomena are not readily explained by current knowledge of circadian systems and suggest that the entrainment process in Siberian hamsters differs markedly from that in other rodent species.


1995 ◽  
Vol 268 (5) ◽  
pp. R1111-R1116 ◽  
Author(s):  
P. Depres-Brummer ◽  
F. Levi ◽  
G. Metzger ◽  
Y. Touitou

In a constant environment, circadian rhythms persist with slightly altered period lengths. Results of studies with continuous light exposure are less clear, because of short exposure durations and single-variable monitoring. This study sought to characterize properties of the oscillator(s) controlling the rat's circadian system by monitoring both body temperature and locomotor activity. We observed that prolonged exposure of male Sprague-Dawley rats to continuous light (LL) systematically induced complete suppression of body temperature and locomotor activity circadian rhythms and their replacement by ultradian rhythms. This was preceded by a transient loss of coupling between both functions. Continuous darkness (DD) restored circadian synchronization of temperature and activity circadian rhythms within 1 wk. The absence of circadian rhythms in LL coincided with a mean sixfold decrease in plasma melatonin and a marked dampening but no abolition of its circadian rhythmicity. Restoration of temperature and activity circadian rhythms in DD was associated with normalization of melatonin rhythm. These results demonstrated a transient internal desynchronization of two simultaneously monitored functions in the rat and suggested the existence of two or more circadian oscillators. Such a hypothesis was further strengthened by the observation of a circadian rhythm in melatonin, despite complete suppression of body temperature and locomotor activity rhythms. This rat model should be useful for investigating the physiology of the circadian timing system as well as to identify agents and schedules having specific pharmacological actions on this system.


1999 ◽  
Vol 277 (3) ◽  
pp. R812-R828 ◽  
Author(s):  
B. Pitrosky ◽  
R. Kirsch ◽  
A. Malan ◽  
E. Mocaer ◽  
P. Pevet

Daily administration of melatonin or S20098, a melatonin agonist, is known to entrain the free-running circadian rhythms of rats. The effects of the duration of administration on entrainment were studied. The animals demonstrated free-running circadian rhythms (running-wheel activity, body temperature, general activity) in constant darkness. Daily infusions of melatonin or S20098 for 1, 8, or 16 h entrained the circadian rhythms to 24 h. Two daily infusions of 1 h (separated by 8 h) entrained the activity peak within the shorter time interval. The entraining properties of melatonin and S20098 were similar and were affected neither by pinealectomy nor by infusion of 1- or 8-h duration. However, with 16-h infusion, less than half of the animals became entrained. Once entrained, the phase angle between the onset of infusion and the rhythms (onset of activity or acrophase of body temperature) increased with the duration of infusion. Before entrainment, the free-running period increased with the duration of infusion, an effect that was not predictable from the phase response curve.


1978 ◽  
Vol 235 (5) ◽  
pp. R243-R249 ◽  
Author(s):  
K. I. Honma ◽  
T. Hiroshige

Three biological rhythms (locomotor activity, body temperature, and plasma corticosterone) were measured simultaneously in individual rats under light-dark cycles and continuous light. Spontaneous locomotor activity was recorded on an Animex and body temperature was telemetrically monitored throughout the experiments. Blood samples were obtained serially at 2-h intervals on the experimental days. Phase angles of these rhythms were calculated by a least-squares spectrum analysis. Under light-dark cycles, the acrophases of locomotor activity, body temperature, and plasma corticosterone were found at 0029, 0106, and 1940 h, respectively. When rats were exposed to 200 lx continuous light, locomotor activity and body temperature showed free-running rhythms with a period of 25.2 h on the average. Plasma corticosterone levels determined at 12 days after exposure to continuous light exhibited a circadian rhythm with the acrophase shifted to 0720. The acrophases of locomotor activity and body temperature, determined simultaneously on the same day, were found to be located at 1303 and 1358 h, respectively. Phase-angle differences among the three rhythms on the 12th day of continuous light were essentially the same with those under the light-dark cycle. These results suggest that circadian rhythms of locomotor activity, body temperature, and plasma corticosterone are most probably coupled to a common internal oscillator in the rat.


2000 ◽  
Vol 164 (1) ◽  
pp. R1-R6 ◽  
Author(s):  
SW Lockley ◽  
DJ Skene ◽  
K James ◽  
K Thapan ◽  
J Wright ◽  
...  

Although melatonin treatment has been shown to phase shift human circadian rhythms, it still remains ambiguous as to whether exogenous melatonin can entrain a free-running circadian system. We have studied seven blind male subjects with no light perception who exhibited free-running urinary 6-sulphatoxymelatonin (aMT6s) and cortisol rhythms. In a single-blind design, five subjects received placebo or 5 mg melatonin p.o. daily at 2100 h for a full circadian cycle (35-71 days). The remaining two subjects also received melatonin (35-62 days) but not placebo. Urinary aMT6s and cortisol (n=7) and core body temperature (n=1) were used as phase markers to assess the effects of melatonin on the During melatonin treatment, four of the seven free-running subjects exhibited a shortening of their cortisol circadian period (tau). Three of these had taus which were statistically indistinguishable from entrainment. In contrast, the remaining three subjects continued to free-run during the melatonin treatment at a similar tau as prior to and following treatment. The efficacy of melatonin to entrain the free-running cortisol rhythms appeared to be dependent on the circadian phase at which the melatonin treatment commenced. These results show for the first time that daily melatonin administration can entrain free-running circadian rhythms in some blind subjects assessed using reliable physiological markers of the circadian system.


1991 ◽  
Vol 261 (4) ◽  
pp. R928-R933 ◽  
Author(s):  
D. M. Edgar ◽  
W. C. Dement

Circadian rhythm entrainment has long been thought to depend exclusively on periodic cues in the external environment. However, evidence now suggests that appropriately timed vigorous activity may also phase shift the circadian clock. Previously it was not known whether levels of exercise/activity associated with spontaneous behavior provided sufficient feedback to phase shift or synchronize circadian rhythms. The present study investigated this issue by monitoring the sleep-wake, drinking, and wheel-running circadian rhythms of mice (Mus musculus) during unrestricted access to running wheels and when free wheel rotation was limited to either 12- or 6-h intervals with a fixed period of 24 h. Wheel rotation was controlled remotely. Mice spontaneously ran in wheels during scheduled access, and free-running sleep-wake and drinking circadian rhythms became entrained to scheduled exercise in 11 of 15 animals. However, steady-state entrainment was achieved only when exercise commenced several hours into the subjective night. The temporal placement of running during entrainment was related (r = 0.7003, P less than 0.02) to free-running period before entrainment. Mice with a free-running period less than 23.0 h did not entrain but exhibited relative coordination between free-running variables and the wheel availability schedule. Thus the circadian timekeeping system responds to temporal feedback arising from the timing of volitional exercise/activity, suggesting that the biological clock not only is responsive to periodic geophysical events in the external environment but also derives physiological feedback from the spontaneous activity behaviors of the organism.


1993 ◽  
Vol 265 (4) ◽  
pp. R951-R956 ◽  
Author(s):  
E. M. Thomas ◽  
M. E. Jewett ◽  
I. Zucker

We investigated the influence of ambient and body temperature (Ta and Tb) on circadian rhythms of gonadectomized male Siberian hamsters. Animals that entered torpor (Tb < 30 degrees C) had significantly shorter circadian periods (tau s) than did nontorpid hamsters at a Ta of 13 degrees C (24.17 +/- 0.05 vs. 24.33 +/- 0.04 h). The tau s of homeothermic hamsters were not affected by Ta change. Short-term decreases in Tb, rather than changes in Ta, appear to affect tau. Access to activity wheels inhibited expression of torpor in short daylengths and was associated with significant increases in body mass. Running wheel activity can mask or block specific short-day responses.


1989 ◽  
Vol 257 (5) ◽  
pp. R1241-R1250 ◽  
Author(s):  
E. M. Thomas ◽  
S. M. Armstrong

Sixteen rats were ovariectomized and given either a 1-cm implant of crystalline estradiol-17 beta (eight rats) or an empty implant (eight rats). A further six rats were sham ovariectomized and given empty implants, and eight rats were left unoperated. The rats were exposed to 70 days of constant dim light (LL) with a maximum illumination level of 20 lx, and circadian running and drinking rhythms were monitored. In LL, both the running and drinking activity rhythms of the ovariectomized, blank-implanted rats became markedly disrupted, whereas unoperated and sham-operated rats maintained unified rhythms. Estradiol-implanted rats developed fewer rhythm desynchronies, and the majority displayed a single band of free-running activity. Rather than being arrhythmic, the activity of the LL-exposed ovariectomized rats appeared to contain several free-running components. Thus these data are consistent with the concept of a multioscillatory basis to the circadian system and support a role for the ovary and its hormone estradiol in the maintenance of coherence between component oscillators.


2007 ◽  
Vol 104 (18) ◽  
pp. 7634-7639 ◽  
Author(s):  
Trinitat Cambras ◽  
John R. Weller ◽  
Montserrat Anglès-Pujoràs ◽  
Michael L. Lee ◽  
Andrea Christopher ◽  
...  

Proper functioning of the human circadian timing system is crucial to physical and mental health. Much of what we know about this system is based on experimental protocols that induce the desynchronization of behavioral and physiological rhythms within individual subjects, but the neural (or extraneural) substrates for such desynchronization are unknown. We have developed an animal model of human internal desynchrony in which rats are exposed to artificially short (22-h) light–dark cycles. Under these conditions, locomotor activity, sleep–wake, and slow-wave sleep (SWS) exhibit two rhythms within individual animals, one entrained to the 22-h light–dark cycle and the other free-running with a period >24 h (τ>24 h). Whereas core body temperature showed two rhythms as well, further analysis indicates this variable oscillates more according to the τ>24 h rhythm than to the 22-h rhythm, and that this oscillation is due to an activity-independent circadian regulation. Paradoxical sleep (PS), on the other hand, shows only one free-running rhythm. Our results show that, similarly to humans, (i) circadian rhythms can be internally dissociated in a controlled and predictable manner in the rat and (ii) the circadian rhythms of sleep–wake and SWS can be desynchronized from the rhythms of PS and core body temperature within individual animals. This model now allows for a deeper understanding of the human timekeeping mechanism, for testing potential therapies for circadian dysrhythmias, and for studying the biology of PS and SWS states in a neurologically intact model.


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