A circulating ghrelin mimetic attenuates light-induced phase delay of mice and light-induced Fos expression in the suprachiasmatic nucleus of rats

Eur J Neurosci. 2008 Apr;27(8):1965-72. doi: 10.1111/j.1460-9568.2008.06181.x. Epub 2008 Apr 10.

Abstract

Anatomical evidence suggests that the ventromedial arcuate nucleus (vmARC) is a route for circulating hormonal communications to the suprachiasmatic nucleus (SCN). Whether this vmARC-SCN connection is involved in the modulation of circadian activity of the SCN is not yet known. We recently demonstrated, in rats, that intravenous (i.v.) injection of a ghrelin mimetic, GHRP-6, during the daytime activated neurons in the vmARC and reduced the normal endogenous daytime Fos expression in the SCN. In the present study we show that i.v. administration of GHRP-6 decreases light-induced Fos expression at ZT13 in the rat SCN by 50%, indicating that light-induced changes in the SCN Fos expression can also be reduced by GHRP-6. Because it is difficult to study light-induced phase changes in rats, we examined the functional effects of GHRP-6 on light-induced phase shifts in mice and demonstrated that peripherally injected GHRP-6 attenuates light-induced phase delays at ZT13 by 45%. However, light-induced Fos expression in the mice SCN was not blocked by GHRP-6. These results illustrate that acute stimulation of the ghrelinergic system may modulate SCN activity, but that its effect on light-induced phase shifts and Fos expression in the SCN might be species related.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Circadian Rhythm / physiology*
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Genes, fos / drug effects*
  • Ghrelin / analogs & derivatives*
  • Light
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Oligopeptides / pharmacology*
  • Rats
  • Rats, Wistar
  • Species Specificity
  • Suprachiasmatic Nucleus / drug effects*
  • Suprachiasmatic Nucleus / metabolism

Substances

  • Ghrelin
  • Oligopeptides
  • growth hormone releasing hexapeptide