Responsiveness to melatonin and its receptor expression in the aging circadian clock of mice.

This study determined the effect of age on the efficacy of melatonin treatment to phase shift circadian activity rhythms and on melatonin receptor expression in the suprachiasmatic nucleus (SCN) and paraventricular nucleus of the thalamus (PVNT) of C3H/HeN mice. The circadian rhythm of 2-[125I]iodomelatonin binding, assessed at three times of the day [circadian times (CT) 2, 10, and 18], showed a modest age-related decrease in the SCN but not the PVNT of old C3H/HeN mice (24 mo). There was a tendency for age to reduce Mel1a melatonin receptor mRNA expression in the suprachiasmatic nucleus during the day, but not during the night. The magnitude of phase shifts of circadian activity rhythms (advances or delays) induced by administration of melatonin at CT 10 or CT 2 was identical in young and old C3H/HeN mice. Together, these results suggest that the decrease in melatonin receptor expression in the SCN had little effect on melatonin-induced phase shifts of circadian activity rhythms. We conclude that the responsiveness of the circadian timing system to melatonin administration does not decrease with age.