Free-Running Activity Rhythms in the Rat: Entrainment by Melatonin

Redman, Jenny; Armstrong, Stuart; Ng, Kim T.

doi:10.1126/science.6823571

Cited by 526 publications

(219 citation statements)

References 15 publications

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“…When 0.5 mg melatonin 424 JOURNAL OF BIOLOGICAL RHYTHMS / October 2003 was started in the phase delay region of the PRC, some individuals did not exhibit changes in phase or period during melatonin administration and continued to free run, again in agreement with the 5-mg studies (Lockley et al, 2000). In contrast to our previous findings, however, we have shown here that when 0.5 mg melatonin is initially administered in the phase delay portion of the PRC, free-running rhythms can eventually become entrained in some individuals when an appropriate circadian time for melatonin administration is reached, analogous to the first study in mammals (Redman et al, 1983). The current study confirms and extends our finding that the CT of administration of melatonin is an important factor in determining whether entrainment occurs (Lockley et al, 2000).…”

Section: Discussionsupporting

confidence: 91%

The Effects of Low-Dose 0.5-mg Melatonin on the Free-Running Circadian Rhythms of Blind Subjects

et al. 2003

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Exogenous melatonin (0.5-10 mg) has been shown to entrain the freerunning circadian rhythms of some blind subjects. The aim of this study was to assess further the entraining effects of a daily dose of 0.5 mg melatonin on the cortisol rhythm and its acute effects on subjective sleep in blind subjects with free-running 6-sulphatoxymelatonin (aMT6s) rhythms (circadian period [τ] 24.23-24.95 h). Ten subjects (9 males) were studied, aged 32 to 65 years, with no conscious light perception (NPL). In a placebo-controlled, single-blind design, subjects received 0.5 mg melatonin or placebo p.o. daily at 2100 h (treatment duration 26-81 days depending on individuals' circadian period). Subjective sleep was assessed from daily sleep and nap diaries. Urinary cortisol and aMT6s were assessed for 24 to 48 h weekly and measured by radioimmunoassay. Seven subjects exhibited an entrained or shortened cortisol period during melatonin treatment. Of these, 4 subjects entrained with a period indistinguishable from 24 h, 2 subjects continued to free run for up to 25 days during melatonin treatment before their cortisol rhythm became entrained, and 1 subject appeared to exhibit a shortened cortisol period throughout melatonin treatment. The subjects who entrained within 7 days did so when melatonin treatment commenced in the phase advance portion of the melatonin PRC (CT6-18). When melatonin treatment ceased, cortisol and aMT6s rhythms free ran at a similar period to before treatment. Three subjects failed to entrain with initial melatonin treatment commencing in the phase delay portion of the PRC. During melatonin treatment, there was a significant increase in nighttime sleep duration and a reduction in the number and duration of daytime naps. The positive effect of melatonin on sleep may be partly due to its acute soporific properties. The findings demonstrate that a daily dose of 0.5 mg melatonin is effective at entraining the free-running circadian systems in most of the blind subjects studied, and that circadian time (CT) of administration of melatonin may be important in determining whether a subject entrains to melatonin treatment. Optimal treatment with melatonin for this non-24-h sleep disorder should correct the underlying circadian disorder (to entrain the sleep-wake cycle) in addition to improving sleep acutely.

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Section: Discussionsupporting

confidence: 91%

The Effects of Low-Dose 0.5-mg Melatonin on the Free-Running Circadian Rhythms of Blind Subjects

et al. 2003

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“…For example, why did the subjects in the present study not entrain once they reached the appropriate advance phase, as would be predicted from the PRC and animal experiments (Redman et al 1983)? A similar lack of entrainment was observed in two sighted subjects by Middleton and colleagues (1997).…”

Section: Figurementioning

confidence: 78%

Melatonin administration can entrain the free-running circadian system of blind subjects

Lockley¹,

Skene²,

James³

et al. 2000

Journal of Endocrinology

245

149

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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 circadian system. 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.

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“…There is increasing evidence that the timing of melatonin secretion is closely associated with the timing of sleep propensity [17] . Melatonin administration shifts circadian rhythms in both rodents [18] and humans [19] and improves sleep by shortening sleep latency and lengthening sleep duration [19] . Melatonin has been used successfully in treating insomnia [20] www.nature.com/aps Tian SW et al Acta Pharmacologica Sinica npg and various circadian rhythm disorders such as delayed sleep phase syndrome [21] and shift-work sleep disorder [22] .…”

Section: Introductionmentioning

confidence: 99%

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

et al. 2010

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Aim: To investigate the potential antidepressant and anxiolytic effects of Neu-P11, a novel melatonin agonist, in two models of depression in rats and a model of anxiety in mice. Methods: In the learned helplessness test (LH), Neu-P11 or melatonin (25-100 mg/kg, ip) was administered to rats 2 h before the beginning of the dark phase once a day for 5 days and the number of escape failures and intertrial crossings during the test phase were recorded. In the forced swimming test (FST), rats received a single or repeated administration of Neu-P11 (25-100 mg/kg, ip). The total period of immobility during the test phase was assessed. In the elevated plus-maze test (EPM), mice were treated with Neu-P11 (25-100 mg/kg, ip) or melatonin in the morning or in the evening and tested 2 h later. The percentage of time spent in the open arms and the open arms entries were assessed. Results: In the LH test, Neu-P11 but not melatonin significantly decreased the escape deficit and had no effect on the intertrial crossings. In the FST, a single or repeated administration of Neu-P11, either in the morning or in the evening, significantly decreased the duration of immobility. In the EPM test, Neu-P11 significantly increased the percentage of time spent in the open arms and the open arms entries irrespective to the time of administration. Melatonin was effective only when administered in the afternoon. Conclusion:The results demonstrate that Neu-P11 exerts antidepressant and anxiolytic activities in rodent models.

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Free-Running Activity Rhythms in the Rat: Entrainment by Melatonin

Cited by 526 publications

References 15 publications

The Effects of Low-Dose 0.5-mg Melatonin on the Free-Running Circadian Rhythms of Blind Subjects

The Effects of Low-Dose 0.5-mg Melatonin on the Free-Running Circadian Rhythms of Blind Subjects

Melatonin administration can entrain the free-running circadian system of blind subjects

Antidepressant- and anxiolytic effects of the novel melatonin agonist Neu-P11 in rodent models

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