Melatonin and sleep: Possible involvement of GABAergic mechanisms

Abstract

Pineal melatonin is synthesized and secreted in close association with the light/dark cycle. The temporal relationship between the nocturnal rise in melatonin secretion and the opening of the sleep gate (i.e., the increase in sleep propensity at the beginning of the night), coupled with the sleep-promoting effects of exogenous melatonin, support the view that endogenous melatonin is involved in the regulation of sleep. The sleep-promoting and sleep-wake rhythm-regulating effects of melatonin are attributed to its action on MT1 and MT2 melatonin receptors present in the suprachiasmatic nucleus (SCN) of the hypothalamus. Nearly all neurons in the SCN contain γ-aminobutyric acid (GABA), and GABA-driven mechanisms have been shown to play a key role in circadian coupling among regions and neurons in the SCN. Results are reviewed indicating that among the neurochemical effects of melatonin in the SCN, its interaction with the GABAergic system appears to be significant for coupling to sleep mechanisms.