Circadian Pattern of Melatonin MT1 and MT2 Receptor Localization in the Rat Suprachiasmatic Nucleus

The suprachiasmatic nucleus (SCN) is the circadian pacemaker. The pineal hormone melatonin is involved in the regulation of circadian phase. As a part of the circadian system its synthesis and secretion is under SCN control. On the other hand, melatonin feeds back on the SCN to regulate its function. Melatonin has two specific windows of time at which it regulates SCN function, namely dusk and dawn. It has been suggested that melatonin exerts its effect on the SCN during that specific window of time via one or both of its specific receptors, MT1 or MT2. The hypothesis that the density of these receptors varies across the circadian cycle was tested. Using immunohistochemistry with receptor-specific antibodies, the localization and distribution of melatonin receptors MT1 and MT2 was studied in the SCN at different circadian times (CT): CT 11–13 (dusk), 23-01 (dawn), 5-7 (mid-day), and 17-19 (midnight). Our results show that MT1 receptor density significantly increased at dusk relative to dawn and midnight (p<0.01 and p<0.001 respectively). Although MT1 receptors were wide spread in the SCN and parts of the optic chiasm at dusk, it was restricted to the SCN during mid-day period. MT2 receptors were not detected in the SCN. In conclusion, melatonin receptor MT1 density and distribution varies with circadian time. This creates a time window at which melatonin exerts its circadian phase shifts on the SCN. This also suggests that melatonin regulates SCN function via MT1 receptors with a minimal role for MT2.