Nocturnal melatonin onset is phase locked to the primary sleep gate

In this study, we used the 'ultrashort sleep-wake paradigm' (7/13), which measures sleep propensity three times an hour for 29 h, from 0700 to 1200 the next day, on 6 healthy male subjects concomitantly with melatonin plasma level. Melatonin was measured once an hour during the morning and early afternoon of the first day and three times an hour from 1600 to 1000 the following morning. Rectal temperature was measured continuously for four subjects. Subjects underwent the 7/13 paradigm three times, and in all three sessions consistent phase relationships were found between the nocturnal onset of melatonin secretion and opening of the nocturnal sleep gate; also, there was an inverse relationship between melatonin and core body temperature and an almost perfect out-of-phase relationship between sleep propensity and temperature, with the temperature peak falling precisely in the middle of the 'forbidden zone' for sleep, i.e., the early evening nadir in sleepiness. On the basis of these phase relationships and previous findings from our laboratory on the effects of exogenous melatonin on the sleep propensity function, we conclude that melatonin participates in sleep-wake regulation in humans.