A cholinergic antagonist, mecamylamine, blocks light-induced Fos immunoreactivity in specific regions of the hamster suprachiasmatic nucleus

Yan Zhang*, Phyllis C. Zee, John D. Kirby, Joseph S. Takahashi, Fred W. Turek

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Recent studies have shown that light-induced phase shifts of the circadian rhythm of locomotor activity are associated with c-fos expression in the suprachiasmatic nucleus (SCN) of rodents. In order to explore further the importance of c-fos expression for the phase-shifting effects of light, we examined the effects of mecamylamine on light-induced Fos-like immunoreactivity (Fos-lir) in the SCN. Mecamylamine was chosen because it is a cholinergic antagonist that blocks the phase-shifting effects of light on the circadian activity rhythm in the golden hamster. Golden hamsters were entrained for at least 14 days to a 14 h light: 10 h dark photoperiod. Animals were then placed in constant darkness (DD) and during exposure to DD were subjected to one or more of the following treatments: (1) vehicle alone; (2) mecamylamine alone (450 μg, i.c.v.) at circadian time (CT) 19; (3) vehicle plus a light pulse at CT 19; (4) mecamylamine 10 min prior to the light pulse at CT 19. Mecamylamine blocked the phase-shifting effects of light on the circadian rhythm of locomotor activity when compared to vehicle-treated animals (P < 0.001). A light pulse at CT 19 induced Fos-lir in the SCN within 1 h, whereas treatment with vehicle or mecamylamine had no noticeable effect on Fos-lir in the SCN. Mecamylamine pretreatment dramatically reduced light-induced Fos-lir in the SCN by 75%. The most striking observation was the clear inhibition of Fos-lir by mecamylamine in the dorsomedial region of the SCN while there was little inhibition of Fos-lir in the most ventral portions of the SCN. These results are consistent with the hypothesis that light-induced phase advances in the activity rhythm are mediated by Fos expression in the SCN, and indicate that Fos expression in the dorsomedial region of the SCN may play a role in light-induced phase shifts in the circadian clock.

Original languageEnglish (US)
Pages (from-to)107-112
Number of pages6
JournalBrain research
Volume615
Issue number1
DOIs
StatePublished - Jun 25 1993

Funding

Acknowledgements. We are grateful to Jon Kornhauser, Martha Vitaterna and Olivier Van Reeth for their help in carrying out these studies. We thank Yvonne Kirby for her help with the statistics and Yu Zhang for his help with the pictures. This work was supported by PHS Grants MH-41211, HD-09885, HD-28048 and NSF STC-8920162.

Keywords

  • Acetylcholine
  • Circadian rhythm
  • Fos immunoreactivity
  • Hamster
  • Mecamylamine

ASJC Scopus subject areas

  • Clinical Neurology
  • Molecular Biology
  • General Neuroscience
  • Developmental Biology

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