Melatonin receptors in the mammalian suprachiasmatic nucleus.

The SCN of the hypothalamus, the site of the circadian pacemaker in mammals, is endowed with melatonin receptors of the ML-1 subtype. Here, we present evidence suggesting that activation of melatonin receptors in the SCN regulates circadian rhythms of behavior in the mouse. In a paradigm simulating a eastbound transmeridian flight, timed administration of melatonin may either accelerate or decrease the rate of reentrainment. Moreover, under constant environmental conditions, exogenous melatonin phase shifts circadian rhythms only during times when the production of the hormone is inhibited. Similarly, light shows periods of circadian sensitivity only at times when light is not present in a natural photoperiod. The maximal phase shifts elicited by melatonin and light coincide with the subjective light-dark (dusk) and subjective dark-light (dawn) transitions. The periods of sensitivity for melatonin, occur at the same circadian times in mouse and in man. Under a short photoperiod the duration of the nocturnal melatonin production may overlap with periods of sensitivity for the hormone, and therefore, melatonin, may be important in synchronizing circadian rhythms to changes in the natural photoperiod. It follows that the identification of periods of circadian sensitivity to melatonin in mammals is important for the development of effective treatments with melatonin and related analogues for sleep disorders characterized by alterations of circadian rhythmicity.