Orphanin-FQ/nociceptin (OFQ/N) modulates the activity of suprachiasmatic nucleus neurons

Charles N. Allen, Zhi Gen Jiang, Koji Teshima, Tristan Darland, Masayuki Ikeda, Cole S. Nelson, Denise I. Quigley, Tohru Yoshioka, Richard G. Allen, Michael A. Rea, David K. Grandy

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Neurons in the suprachiasmatic nucleus (SCN) constitute the principal circadian pacemaker of mammals. In situ hybridization studies revealed expression of orphanin-FQ/nociceptin (OFQ/N) receptor (NOR) mRNA in the SCN, whereas no expression of mRNA for preproOFQ/N (ppOFQ/N) was detected. The presence of OFQ/N peptide in the SCN was demonstrated by radioimmunoassay. SCN neurons (88%) responded dose-dependently to OFQ/N with an outward current (EC50 = 22.3 nM) that was reduced in amplitude by membrane hyperpolarization and reversed polarity near the theoretical potassium equilibrium potential. [Phe1 ψ(Ch2-NH)Gly2]OFQ/N(1-13)NH2 (3 μM), a putative NOR antagonist, activated a small outward current and significantly reduced the amplitude of the OFQ/N-stimulated current. OFQ/N reduced the NMDA receptor-mediated increase in intracellular Ca2+. When injected unilaterally into the SCN of Syrian hamsters housed in constant darkness, OFQ/N (1-50 pmol) failed to alter the timing of the hamsters' wheel-running activity. However, injection of OFQ/N (0.1-50 pmol) before a brief exposure to light during the mid-subjective night significantly attenuated the light- induced phase advances of the activity rhythm. These data are consistent with the interpretation that OFQ/N acting at specific receptors modulates the activity of SCN neurons and, thereby, the response of the circadian clock to light.

Original languageEnglish (US)
Pages (from-to)2152-2160
Number of pages9
JournalJournal of Neuroscience
Volume19
Issue number6
DOIs
StatePublished - Mar 15 1999

Keywords

  • Calcium
  • Circadian rhythm
  • Nociceptin
  • Orphanin-FQ
  • Potassium current
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)

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