Abstract
Circadian rhythms are known to be entrained to the 24h day primarily by the light-dark cycle. In the increasing urban population many individuals have limited exposure to natural daylight, particularly in the temperate regions where daylength is extended by artificial light. In constant low level illumination humans exhibit free-running rhythms with periods usually in excess of 24h. The main aim of this thesis was to investigate the ability of timed melatonin administration and/or scheduled light:dark cycles of varying intensity to prevent free-run or to resynchronise already free-running rhythms. An isolation unit equipped with a controlled lighting system, where subjects could be maintained as a group, was used for all the studies reported. A baseline study ascertained that sighted, normal, healthy males would exhibit free-running rhythms when maintained as a group in constant dim light, but with knowledge of clock time. The subjects did not synchronise as a group but displayed distinct individual periods. The average endogenous tau, as measured by core body temperature and urinary 6- sulphatoxymelatonin, was 24.26+/-0.05h. 5mg melatonin administered at 20:00h had weak zeitgeber effects. When given as a first treatment, shortly after entering the isolation unit, it was able to maintain apparent synchrony (or “stabilisation”) of the sleep-wake cycle to 24h. The core body temperature rhythm was not convincingly synchronised and in some individuals the demasked temperature tau appeared to be shortened by the melatonin treatment. When administered to already free-running individuals, 5mg melatonin at 20:00h was able to resynchronise the sleep-wake cycle by phase advance. It was less successful at re-entraining rhythms by phase delay. The direction of resynchronisation was dependent on the circadian time of administration as predicted by the PRC for melatonin. Mathematical demasking of the temperature data did not affect the calculated overall periodicity although it did alter the acrophase time. 12:12 light-dark cycles of 20 lux and 200 lux intensity were unable to maintain synchrony of human circadian rhythms to 24h. 1000 lux was able to prevent free-run but was not able to resynchronise already free-running rhythms convincingly. This was possibly due to an insufficiently long time series. Combined melatonin administration and 1000 lux lighting schedule maintained entrainment to 24h in all the parameters measured. There was significantly less variance in the data than with melatonin alone, but little if any difference when compared to 1000 lux alone. Under certain conditions melatonin administration caused fragmented sleep patterns. This was possibly due to the timing of the dose in relation to the temperature rhythm. A further experiment was carried out to test this hypothesis, and irregular sleep was seen in 4/6 individuals. Overall this thesis suggests that melatonin has useful “chronobiotic” properties. It was most effective when combined with light treatment.