Melatonin and maturation of REM sleep.

The discovery in 1953 of rapid eye movement (REM) sleep and the appreciation that sleep is a heterogeneous physiological state stimulated major research into sleep disorders. Electroencephalographic studies have shown that the amount of REM sleep changes with age. While newborns spend almost 50% of their sleep time in REM, the percentage of REM sleep decreases to 30% by the age of 3 months and to 20% by the age of 6 months. In addition, newborns enter REM sleep soon after the initiation of sleep, but by the age of 4 months entry into sleep assumes the adult pattern in which a significant period of non-REM sleep precedes the onset of REM sleep. Since reduction in the amount of REM sleep is associated with cerebral maturation and since the pineal gland has been implicated both in cerebral development and in the organization of REM sleep, the pineal gland may be involved in the maturation of the adult REM sleep pattern. Prior to the age of 3 months melatonin plasma levels are low and the characteristic circadian rhythms of melatonin are absent. Thereafter, melatonin secretion increases and circadian rhythmicity of melatonin becomes apparent. Thus, the abundance of REM sleep during the first 3 months of infancy is associated with deficient pineal melatonin functions, while the decline in the percentage of REM sleep coincides with the emergence of melatonin secretion coincident with the maturation of the pineal gland. I propose, therefore, that a state of low melatonin secretion is permissive for REM sleep and that maturation of the pineal gland retards REM sleep. This hypothesis is supported by the findings that melatonin suppresses REM sleep in cats and that in rats and humans pinealectomy induces a narcoleptic-like pattern of REM sleep which strikingly resembles that of the newborn and which is reversed by the administration of melatonin. A further hypothesis is advanced to explain the pathophysiology of narcolepsy in terms of a maturational defect of the pineal gland in infancy.