Melatonin: role in gating nocturnal rise in sleep propensity

The present article reviews the evidence that melatonin possesses sleep-inducing effects and that it gates the increase in nocturnal sleepiness. It is shown that, without exception, all the studies that have investigated daytime administrations of melatonin reported increased sleepiness, even at doses that do not increase plasma levels of melatonin beyond its physiological levels. By contrast, nighttime increase in sleepiness was achieved only after administration of high doses. Based on these findings and on the precise coupling between the endogenous nocturnal increase in melatonin secretion and the opening of the sleep gate, it is suggested that melatonin participates in the regulation of the sleep-wake cycle by inhibiting the central nervous system wakefulness generating system. This inhibition allows a smooth transition from wakefulness to sleep. Clinical findings on decreased levels of nocturnal melatonin in chronic insomniacs, and on the efficacy of exogenous melatonin in improving sleep in melatonin-deficient insomniacs, are congruent with this hypothesis.