Melatonin As A Phaseresetting Agen

In some animals, exogenous melatonin causes phase shifts and can even provide an entraining signal (see above). Early work by Arendt suggested that melatonin could intermittently have phase-advancing effects (48). Blind people appear to be even more sensitive to these effects than sighted people, perhaps because they are not affected by a competing light/dark cycle (49-51). Eventually, a melatonin PRC (four days of administering 0.5mg) was described in sighted people that for the first time: 1) showed consistent and robust phase advances; 2) demonstrated phase delays; and 3) described the relationship between the time of melatonin administration and the direction of phase shift (52). These phase shifts were smaller in sighted people, because melatonin had to override the effects of a light/dark cycle which was held constant. The magnitude of these phase shifts increases ten-fold when the sleep/wake and ambient light/dark cycles are shifted 12 hours (53), as is the case with the light PRC study that showed the greatest phase shifts (20). Subsequently, it was shown that these phase shifts can be achieved within one day (54-55) and that these effects are dose-dependent (55).

The original melatonin PRC study has been replicated by another group of investigators (54). Furthermore, an interim report of an additional six subjects given mela-tonin for 12 trials at times two hours apart showed a PRC similar to the original (28,56). The complete study of 12 subjects (manuscript in preparation) confirms the interim report. In all three PRCs (obtained using a small oral dose of melatonin), the crossover time between advances and delays appears to be at about CT 18 and between delays and advances at about CT 6. [Because of inter-individual variation in internal body clock time, circadian time (CT) is determined by the baseline DLMO (CT 14), since it usually occurs about 14 hours after sleep offset (lights on).]

Figure 3. The binned melatonin (closed squares) and light (open squares) PRCs plotted together.The phase-shift magnitudes for the Czeisler's group light PRC (20), which has been adapted from the PRC Atlas (58), have been divided by ten, so that circadian phase positions of the two PRCs can be more easily compared. The scale on the abscissa has been shifted 12 hours for the light PRC. The overlap of the data is quite striking that indicates that the two PRCs are about 12 hours out of phase with each other. From Lewy et al. (56) with permission.

Figure 3. The binned melatonin (closed squares) and light (open squares) PRCs plotted together.The phase-shift magnitudes for the Czeisler's group light PRC (20), which has been adapted from the PRC Atlas (58), have been divided by ten, so that circadian phase positions of the two PRCs can be more easily compared. The scale on the abscissa has been shifted 12 hours for the light PRC. The overlap of the data is quite striking that indicates that the two PRCs are about 12 hours out of phase with each other. From Lewy et al. (56) with permission.

Therefore, the melatonin and light PRCs appear to be about 12 hours out of phase with each other (Figure 3) (56). This suggests that one function of endogenous melatonin may be to augment entrainment of the ECP by the light/dark cycle. When given to shift workers, the melatonin PRC has a similar shape, but the phase-shift magnitudes (as mentioned above) are ten times greater (53). Perhaps, melatonin and darkness potentiate each other's phase-shifting effects: a second function of melatonin may be to help the ECP discriminate between nighttime darkness and sporadic daytime naps, conferring more zeitgeber strength to the former (57). This may explain why melatonin is not produced when darkness occurs in the middle of the day.

Natural Cures For Insomnia

Natural Cures For Insomnia

How Would You Love To Finally Get A Decent Night's Sleep? Do you toss and turn all night long without getting much of a wink of sleep? Are you tired of counting sheep for hours without falling asleep? Wouldn't you love to be able to fall asleep simply, easily and naturally, without pills, potions or harmful medicine?

Get My Free Ebook


Post a comment