Reentrainment of Rat Circadian Activity Rhythms: Effects of Melatonin
TL;DR: Daily melatonin injections administered at the old dark onset did not alter direction of reentraining transients but decreased latency to reach steady‐state entrainment, and the time of day of melatonin administration appears to be a critical factor in its mode of action.
Abstract: Experiments were conducted to determine whether daily melatonin injections could influence reentrainment of circadian locomotor activity rhythms in male Long-Evans rats after phase shifts of the light dark (LD) cycle. When exposed to a 5-h advance of the LD cycle, six out of 15 rats injected daily with melatonin at the new dark onset reentrained by a phase delay of the activity rhythm. The remaining nine melatonin-injected rats and 14 of the 15 control injected rats phase advanced. Daily melatonin injections administered at the old dark onset did not alter direction of reentraining transients but decreased latency to reach steady-state entrainment. In contrast, the effects of melatonin injections given at the end of both the old and new dark periods are difficult to interpret due to the effects of the injection procedure itself at these times. Following an 8-h advance of the LD cycle, all melatonin-injected rats phase advanced while all vehicle and uninjected control rats phase delayed when injections were given at the old dark onset. As has been found in other research areas, the time of day of melatonin administration appears to be a critical factor in its mode of action. It is yet to be established whether these results from the use of pharmacological doses of melatonin are indicative of endogenous melatonin's involvement in the circadian reentrainment mechanism.
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TL;DR: Within recent years, many investigators have implicated the pineal gland and melatonin in the processes of both aging and age-related diseases, with one theory assuming that the waning melatonin cycle provides an important switch for genetically programmed aging at the cellular level.
283 citations
TL;DR: The effects of melatonin in rodent behavior are described, focusing on inhibitory effects (sedation, hypnotic activity, pain perception threshold elevation), and direct effects on circadian rhythmicity (entrainment, resynchronization, alleviation of jet-lag symptoms, phase-shifting).
203 citations
TL;DR: Results suggest that melatonin is a potent synchronizer of rat circadian rhythms and has a direct action on the circadian pacemaker, possibly acting as an internal zeitgeber for the total circadian structure of mammals.
Abstract: Although pinealectomy has little influence on the circadian locomotor rhythms of laboratory rats, administration of the pineal hormone melatonin has profound effects. Evidence for this comes from studies in which pharmacological doses of melatonin are administered under conditions of external desynchronization, internal desynchronization, steady state light-dark conditions, and phase shifts of the zeitgeber. Taken together with recent findings on melatonin receptor concentration in the rat hypothalamus, particularly at the level of the suprachiasmatic nuclei, these results suggest that melatonin is a potent synchronizer of rat circadian rhythms and has a direct action on the circadian pacemaker. It is possible, therefore, that the natural role of endogenous melatonin is to act as an internal zeitgeber for the total circadian structure of mammals at the level of cell, tissue, organ, whole organism and interaction of that organism with environmental photoperiod changes.
197 citations
TL;DR: Both human and animal studies suggest that MLT has powerful chronobiotic properties and shows considerable promise as a prophylactic and therapeutic alternative or supplement to the use of natural and artificial bright light for resetting the circadian pacemaker.
151 citations
TL;DR: The suprachiasmatic nuclei appear to be an important site for the entrainment effect of Mel and the presence of Mel receptors appears to be a prerequisite, however, the pharmacological dose of Mel needed to entrain circadian rhythms means that very probably other sites and mechanisms also play a role.
Abstract: In mammals, the exact role of melatonin (Mel) in the circadian timing system remains to be determined. However, exogenously administered Mel, as reported in the present mini-review, has been shown to affect the circadian clock. The sites and mechanisms of action involved in this "chronobiotic" effect of Mel have begun to be characterized. The suprachiasmatic nuclei (SCN) appear to be an important site for the entrainment effect of Mel and the presence of Mel receptors appears to be a prerequisite. However, the pharmacological dose of Mel needed to entrain circadian rhythms means that very probably other sites and mechanisms also play a role.
146 citations
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TL;DR: The pineal gland hormone melatonin may play a role in synchronization of rat circadian rhythms, and the time of day of melatonin administration is crucial in pharmacological experiments.
Abstract: The pineal gland hormone melatonin may play a role in synchronization of rat circadian rhythms. Free-running activity rhythms of the rat were entrained by a daily melatonin injection, with entrainment occurring when the onset of activity coincided with the time of daily injections. When injections were stopped, activity rhythms became free-running again. Thus in pharmacological experiments, the time of day of melatonin administration is crucial.
552 citations
TL;DR: The data demonstrate that the pineal organ is a crucial component of the endogenous time-measuring system of the sparrow, and does not abolish the rhythm of locomotor activity in birds exposed to light-dark cycles.
Abstract: The pineal organ of the house sparrow, Passer domesticus, is essential for persistence of the circadian locomotor rhythm in constant conditions. Upon removal of the pineal body, activity becomes arrhythmic. However, pinealectomy does not abolish the rhythm of locomotor activity in birds exposed to light-dark cycles. Pinealectomized birds are entrained by light cycles in much the same manner as are normal birds. Our data demonstrate that the pineal organ is a crucial component of the endogenous time-measuring system of the sparrow.
357 citations
01 Jan 1975
TL;DR: To describe anabrupt shift of the Zeitgeber sufficiently, it is necessary to indicate whether the phase has been advanced or delayed, for how many hours it has been shifted, and what part of theZeitgeber has been lengthened or shortened respectively.
Abstract: To describe anabrupt shift of the Zeitgeber sufficiently, it is necessary to indicate whether the phase has been advanced or delayed, for how many hours it has been shifted, and what part of the Zeitgeber has been lengthened or shortened respectively. The entrained circadian system usually follows a shift of the Zeitgeber in the same direction and by an equal amount. However, there can be exceptions to both of these rules: a) an instantaneous 12-h shift of a (symmertric) Zeitgeber always represents a delya (= doubling of one-half of its period). In contrast to this, the gradual re-entrainment of the circadian system can be accompalished by either advances or by delays (Fig. 2), it can occur in both dirctions simultaneously by splitting the rhythmic variable (Fig. 1),or it can represent an apparent advance not distinghushable from a delay ( Fig. 6); b) after complietion of re-entraiment, the phase-angle difference psi between organism and Zeitgeber an differ systematically from the pre-shift psi-value...
356 citations
TL;DR: The data suggest that the behavioral effects of melatonin, like those on reproduction in seasonally breeding mammals, depend upon an intact circadian system and the SCN.
233 citations
TL;DR: The results indicate that daily MEL injections are capable of suppressing reproductive physiology in male hamsters, but only when the indole is injected late in the light period, in this case, 13 h after light on.
Abstract: The daily s.c. injection of 25 µg melatonin (MEL) in oil into adult male hamsters at 7 p.m. (lights on 6 a.m. to 8 p.m.) for 50 days caused involution of the testes, coagulation of
168 citations