THE ROLE OF PINEAL MELATONIN IN SLEEP REGULATION

Melatonin (N-acetyl-5-methoxytryptamine) is a phylogenetically primitive molecule, found in such diverse species as unicellular organisms, plants and vertebrates. In vertebrate animals, the main source of melatonin is the pineal gland (epiphysis cerebri). There are indirect signs of a close relationship between melatonin and sleep in humans. For example, the hours of the increased melatonin secretion are concurrent with the habitual hours of sleep, the onset of melatonin secretion correlates with the onset of evening sleepiness. Furthermore, melatonin treatment is typically found to produce subjective and/or objective sleep-promoting effects in healthy research subjects when administered during the day or to improve overnight sleep in insomniacs. These effects are observed in response to doses that induce physiological (i.e., around 100 pg/ml) and pharmacological (over 200 pg/ml) circulating levels of the hormone. Remarkably, the effects of both physiological and pharmacological doses of melatonin are not accompanied by any dramatic changes in electrophysiological sleep architecture, a common complication encountered with many existing hypnotics and anxiolytics. Collectively, the available data on the effects of melatonin on sleep suggest that a nocturnal surge in melatonin production may be an important factor in normal human sleep regulation, and that melatonin deficiency might contribute to an altered sleep pattern. The understanding of the mechanisms of action of melatonin at the cellular level has advanced substantially over the last few years, especially following cloning of a family of G protein-coupled melatonin receptors. Our recent studies in several animal models have also shown that melatonin has a hypnotic-like property in diverse species, from primates to fish, and that this effect is mediated via specific melatonin receptors. Further studies on the nature of melatonin s sleep-promoting effects might contribute to a better understanding of the mechanisms of sleep regulation.