Pinealectomized Rats Entrain and Phase-Shift to Melatonin Injections in a Dose-Dependent Manner

Wade S. Warren, Donald B. Hodges, Vincent M. Cassone

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65 Scopus citations


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 (with a median effective dose [ED50] of 5.45 ± 1.33 μg/kg) and in constant bright light. 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 ± 53 ng/kg and 121 ± 22 ng/kg for SHAM and PINX rats, respectively, during the entrainment experiment. The ED50's 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 mg/kg melatonin has previously been shown to cause a phase advance of approximately 45 min when administered at about circadian time (CT) 10. We found that both SHAM and PINX animals phase-advanced, in a dose-dependent manner to a single melatonin injection given at CT 10. The data for the phase-shifting experiment indicated an ED50 of 8.19 ± 0.572 μg/kg and 2.16 ± 0.326 μg/kg for SHAM and PINX animals, respectively, with an average phase advance of 40 min 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 controls.

Original languageEnglish
Pages (from-to)233-245
Number of pages13
JournalJournal of Biological Rhythms
Issue number3
StatePublished - Oct 1993


  • circadian
  • dose-response
  • median effective dose

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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