title: Phase shifts to light are altered by antagonists to neuropeptide receptors.
abstract: The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is a heterogeneous structure. Two key populations of cells that receive retinal input and are believed to participate in circadian responses to light are cells that contain vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP). VIP acts primarily through the VPAC2 receptor, while GRP works primarily through the BB2 receptor. Both VIP and GRP phase shift the circadian clock in a manner similar to light when applied to the SCN, both in vivo and in vitro, indicating that they are sufficient to elicit photic-like phase shifts. However, it is not known if they are necessary signals for light to elicit phase shifts. Here we test the hypothesis that GRP and VIP are necessary signaling components for the photic phase shifting of the hamster circadian clock by examining two antagonists for each of these neuropeptides. The BB2 antagonist PD176252 had no effect on light-induced delays on its own, while the BB2 antagonist RC-3095 had the unexpected effect of significantly potentiating both phase delays and advances. Neither of the VIP antagonists ([d-p-Cl-Phe6, Leu17]-VIP, or PG99-465) altered phase shifting responses to light on their own. When the BB2 antagonist PD176252 and the VPAC2 antagonist PG99-465 were delivered together to the SCN, phase delays were significantly attenuated. These results indicate that photic phase shifting requires participation of either VIP or GRP; phase shifts to light are only impaired when signalling in both pathways are inhibited. Additionally, the unexpected potentiation of light-induced phase shifts by RC-3095 should be investigated further for potential chronobiotic applications.
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Chan
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Psychology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Sterniczuk
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Yaruuna
authors.initials: Y
authors.lastname: Enkhbold
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Jeffers
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Priyoneel
authors.initials: P
authors.lastname: Basu
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Duong
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Sue-Len
authors.initials: SL
authors.lastname: Chow
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Smith
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada. Electronic address: antlem@ucalgary.ca.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Antle
mesh_terms: D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology; D006224:Cricetinae; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D008027:Light; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010775:Photic Stimulation / Q000379:methods; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D018013:Receptors, Neuropeptide; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D014660:Vasoactive Intestinal Peptide; D019886:Gastrin-Releasing Peptide; D001839:Bombesin
keywords: bombesin; core; network; rodent; shell