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Journal of Neuroscience, Vol 15, 5612-5622, Copyright © 1995 by Society for Neuroscience
Neuropeptides phase shift the mammalian circadian pacemaker
HD Piggins, MC Antle and B Rusak
Department of Psychology, Dalhousie University, Halifax, Nova Scotia, Canada.
We studied the influence on circadian rhythms of peptides that have been
reported to be colocalized in suprachiasmatic nucleus (SCN) neurons.
Gastrin-releasing peptide (GRP1-27), peptide histidine isoleucine (PHI),
and vasoactive intestinal polypeptide (VIP) were microinjected into the
suprachiasmatic nucleus (SCN) region of Syrian hamsters free running under
three different constant lighting conditions. All peptide injections caused
phase-dependent phase shifts of hamster locomotor activity rhythms which
were unaffected by constant lighting conditions. GRP1-27 (150 pmol) caused
large phase delays when injected at circadian times (CT) 12-16, modest
phase advances when administered at CT20-24, and few shifts during the
subjective day. Injections of saline vehicle at any of these phases caused
only very small phase shifts. Phase delays induced by GRP1-27 at CT12-14
were dose dependent, unrelated to injection volume (at a constant dose),
and attenuated by pretreatment with the BN/GRP-preferring receptor
antagonist BIM 26226. VIP (150 pmol) caused moderate phase delays at
CT12-14 and moderate phase advances at CT20-24. PHI (150 pmol) caused
moderate phase delays at CT12-14 only. Coadministration of 150 pmol of
GRP1-27, PHI, and VIP in an equimolar neuropeptide cocktail (50 pmol of
each peptide) caused phase delays at CT12-14 and phase advances at CT20- 24
which did not differ from those induced by 150 pmol of GRP1-27 alone at
these phases. The shifts induced by 150 pmol of the peptide cocktail were
smaller than the sum of the shifts induced by 50 pmol doses of each peptide
administered separately at those phases. Since the phase- delaying effects
of the cocktail were weaker than the summed effects of the component 50
pmol doses of the peptides, these data demonstrate a lack of synergism
among the effects of these peptides. Since GRP1-27 (150 pmol) evoked shifts
similar in magnitude to those of the cocktail, there is no evidence that
these apparently colocalized neuropeptides must interact to exert maximal
effects on the circadian pacemaker.
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