The effects of aging and chronic fluoxetine treatment on circadian rhythms and suprachiasmatic nucleus expression of neuropeptide genes and 5-HT 1B receptors

Marilyn J. Duncan, James M. Hester, Jason A. Hopper, Kathleen M. Franklin

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Age-related changes in circadian rhythms, including attenuation of photic phase shifts, are associated with changes in the central pacemaker in the suprachiasmatic nucleus (SCN). Aging decreases expression of mRNA for vasoactive intestinal peptide (VIP), a key neuropeptide for rhythm generation and photic phase shifts, and increases expression of serotonin transporters and 5-HT 1B receptors, whose activation inhibits these phase shifts. Here we describe studies in hamsters showing that aging decreases SCN expression of mRNA for gastrin-releasing peptide, which also modulates photic phase resetting. Because serotonin innervation trophically supports SCN VIP mRNA expression, and serotonin transporters decrease extracellular serotonin, we predicted that chronic administration of the serotonin-selective reuptake inhibitor, fluoxetine, would attenuate the age-related changes in SCN VIP mRNA expression and 5-HT1B receptors. In situ hybridization studies showed that fluoxetine treatment does not alter SCN VIP mRNA expression, in either age group, at zeitgeber time (ZT)6 or 13 (ZT12 corresponds to lights off). However, receptor autoradiographic studies showed that fluoxetine prevents the age-related increase in SCN 5-HT1B receptors at ZT6, and decreases SCN 5-HT1B receptors in both ages at ZT13. Therefore, aging effects on SCN VIP mRNA and SCN 5-HT1B receptors are differentially regulated; the age-related increase in serotonin transporter sites mediates the latter but not the former. The studies also showed that aging and chronic fluoxetine treatment decrease total daily wheel running without altering the phase of the circadian wheel running rhythm, in contrast to previous reports of phase resetting by acute fluoxetine treatment.

Original languageEnglish
Pages (from-to)1646-1654
Number of pages9
JournalEuropean Journal of Neuroscience
Volume31
Issue number9
DOIs
StatePublished - May 2010

Keywords

  • Gastrin releasing peptide
  • Hamster
  • SSRI
  • Serotonin selective reuptake inhibitor
  • Vasoactive intestinal peptide

ASJC Scopus subject areas

  • Neuroscience (all)

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