Extended action of MKC-242, a selective 5-HT1A receptor agonist, on light-induced Per gene expression in the suprachiasmatic nucleus in mice

Satomi Takahashi, Yuko Yoshinobu, Reiko Aida, Haruka Shimomura, Masashi Akiyama, Takahiro Moriya, Shigenobu Shibata

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

We reported previously that (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole hydrochloride (MKC-242) (3 mg kg-1, i.p.), a selective 5-HT1A receptor agonist, accelerated the re-entrainment of hamster wheel-running rhythms to a new 8 hr delayed or advanced light-dark cycle, and also potentiated the phase advance of the wheel-running rhythm produced by light pulses. The molecular mechanism underlying MKC-242-induced potentiation of this phase shift, however, has not yet been elucidated. We examined the effects of MKC-242 on light-induced mPer1 and mPer2 mRNA expression in the suprachiasmatic nucleus (SCN) of mice. MKC-242 (5 mg kg-1, i.p.) potentiated light-induced mPer1 and mPer2 expression in the SCN of mice housed in constant darkness for 2 days, when mRNA levels were observed 3 hr after light-exposure. More potentiating action of MKC-242 on mPer2 expression in the SCN was observed in mice housed in constant darkness for 9-10 days. This facilitatory action of MKC-242 on mPer1 expression was antagonized by WAY100635, a selective 5-HT1A receptor blocker, indicating that MKC-242 activated 5-HT1A receptors. Other drugs such as 8-hydroxy-dipropylaminotetralin (10 mg kg-1, i.p.), paroxetine (10 mg kg-1, i.p.), buspirone (10 mg kg-1, i.p.), and diazepam (10 mg kg-1, i.p.) did not display a potentiating action on light-induced mPer1 and mPer2 expression in the SCN. In the behavioral experiments, we found that MKC-242 (5 mg kg-1, i.p.) potentiated light-induced phase delays of free-running rhythm in mice. The present results suggest that prolonged increase of mPer1 or mPer2 expression in the SCN by MKC-242 may be involved in the potentiation of photic entrainment by MKC-242 in mice.

Original languageEnglish
Pages (from-to)470-478
Number of pages9
JournalJournal of Neuroscience Research
Volume68
Issue number4
DOIs
Publication statusPublished - 2002 May 15

Keywords

  • 5-HT receptor
  • Circadian rhythm
  • Light-entrainment
  • MKC-242
  • Per gene
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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