Response of the mouse circadian system to serotonin 1A/2/7 agonists in vivo: Surprisingly little

Michael C. Antle, Malcolm D. Ogilvie, Gary E. Pickard, Ralph E. Mistlberger

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Serotonin (5-HT) is thought to play a role in regulating nonphotic phase shifts and modulating photic phase shifts of the mammalian circadian system, but results with different species (rats vs. hamsters) and techniques (in vivo vs. in vitro; systemic vs. intracerebral drug delivery) have been discordant. Here we examined the effects of the 5-HT1A/7 agonist 8-OH-DPAT and the 5-HT1/2 agonist quipazine on the circadian system in mice, with some parallel experiments conducted with hamsters for comparative purposes. In mice, neither drug, delivered systemically at a range of circadian phases and doses, induced phase shifts significantly different from vehicle injections. In hamsters, quipazine intraperitoneally (i.p.) did not induce phase shifts, whereas 8-OH-DPAT induced phase shifts after i.p. but not intra-SCN injections. In mice, quipazine modestly increased c-Fos expression in the SCN (site of the circadian pacemaker) during the subjective day, whereas 8-OH-DPAT did not affect SCN c-Fos. In hamsters, both drugs suppressed SCN c-Fos in the subjective day. In both species, both drugs strongly induced c-Fos in the paraventricular nucleus (within-subject positive control). 8-OH-DPAT did not significantly attenuate light-induced phase shifts in mice but did in hamsters (between-species positive control). These results indicate that in the intact mouse in vivo, acute activation of 5-HT1A/2/7 receptors in the circadian system is not sufficient to reset the SCN pacemaker or to oppose phase-shifting effects of light. There appear to be significant species differences in the susceptibility of the circadian system to modulation by systemically delivered serotonergics.

Original languageEnglish (US)
Pages (from-to)145-158
Number of pages14
JournalJournal of Biological Rhythms
Issue number2
StatePublished - Apr 1 2003
Externally publishedYes


  • 8-OH-DPAT
  • Fos
  • Hamster
  • Mouse
  • PRC
  • Phase shift
  • Quipazine
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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