Melatonin, the Pineal Gland, and Circadian Rhythms

Previous work has shown that daily injections of the pineal hormone melatonin N- acetyl, 5 methoxytryptamine entrain the free-running locomotor rhythms of rats held in constant darkness DD with a median effective dose ED50 of 5.45 plus or minus 1.33 microgramkg and in constant bright light LL. The present experiments determined the dose-response characteristics of entrainment and phase-shifting to daily and single melatonin injections in both sham operated SHAM and pinealectomized PINX rats. The data indicated an ED50 of 332 plus or minus 53 ngkg and 121 plus or minus 22 ngkg for SHAM and PINX rats respectively during the entrainment experiment. The ED50s for the entrainment experiment were considerably lower than doses previously employed and much lower than doses employed in reproductive and metabolic studies in rats and hamsters. The data indicated that no partial entrainment - occurred, nor were there differences in phase angle, length of activity or period among all effective doses. Next, a single injection of 1 microgramkg melatonin has previously been shown to cause a phase-advance of approximately 45 minutes when administered around circadian time CT 10. We found that both SHAM and PINX animals phase-advanced to a single melatonin injection given at CT10 in a dose-dependent manner. The data for the phase- shifting experiment indicated a median effective dose of 8.19 plus or minus 0.572 microgramkg and 2.16 plus or minus .326 microgramkg for SHAM and PINX animals respectively with an average phase advance of 40 minutes for both groups. Together, the data suggest that the presence of the pineal gland is not necessary for the effects of melatonin on the rat circadian system and that PINX animals are marginally more sensitive to melatonin than their SHAM operated controls.