Pituitary adenylate cyclase-activating polypeptide produces a phase shift associated with induction of mPer expression in the mouse suprachiasmatic nucleus

Y. Minami, K. Furuno, M. Akiyama, T. Moriya, S. Shibata

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The main mammalian circadian pacemaker is located in the suprachiasmatic nucleus of the hypothalamus. Clock genes such as the mouse Period gene (mPer) play a role in this core clock mechanism in the mouse. With brief light exposure during the subjective night, the photic information, which is conveyed directly to the suprachiasmatic nucleus via the retinohypothalamic tract, results in mPer1 and mPer2 expression in the suprachiasmatic nucleus. Glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) are co-stored in the retinohypothalamic tract. Recent studies have suggested that not only glutamate but also PACAP are key players in the phase shift that occurs during subject night; however, research demonstrating a direct association between the PACAP-induced phase shift and mPer gene expression has yet to be conducted. In the present study, PACAP (200 pmol) injected into the lateral ventricle during subjective night (circadian time 16; circadian time 12, onset of locomotor activity) caused a moderate phase delay associated with moderate expression of mPer1 and only slight expression of mPer2 in the mouse suprachiasmatic nucleus. PACAP-induced mPer1 expression was also observed in the paraventricular nucleus and periventricular area of the hypothalamus. (+)MK-801 (0.5 mg/kg), an N-methyl-D-aspartate (NMDA) receptor antagonist, suppressed both the PACAP-induced phase delay and mPer1 expression. From these results we suggest that PACAP induces phase delays in the mouse circadian rhythm in association with an increase of mPer expression in the suprachiasmatic nucleus via the activation of NMDA receptors.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
Issue number1
Publication statusPublished - 2002 Aug 2



  • (+)MK-801
  • Circadian rhythm
  • Entrainment
  • NMDA receptor
  • i.c.v. injection

ASJC Scopus subject areas

  • Neuroscience(all)

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