title: An NMDA antagonist inhibits light but not GRP-induced phase shifts when administered after the phase-shifting stimulus.
abstract: Brief light pulses or microinjection of gastrin-releasing peptide (GRP) into the third ventricle or near the suprachiasmatic nucleus (SCN) induce phase shifts of circadian rhythms during the subjective night. It has previously been reported that these effects are strongly influenced by the activation of N-methyl-d-aspartate (NMDA) receptors and the availability of glutamate. We hypothesized that the photic signaling pathway in the SCN was dependent on glutamate neurotransmission even after the completion of a photic stimulus. Adult male Syrian hamsters equipped with a surgically implanted guide cannula aimed at the SCN region were housed in constant darkness until stable free-running rhythms of wheel-running activity were apparent. Light pulses administered in the early night induced phase delays of circadian rhythms which were attenuated by the co-administration of (+/-)-2-amino-5-phosphonopentanoic acid (AP5), an NMDA antagonist. Microinjection of AP5 also inhibited light-induced shifts, to a lesser extent, immediately after and 15 min after, but not 30 min after the light pulse. A second experiment was designed to test whether AP5 would be able to attenuate GRP-induced shifts 15 min following microinjection of GRP. Phase shifts of animals that received microinjection of AP5 15 min after the administration of GRP were not different from those that received microinjection of GRP and vehicle. These data suggest that glutamate signaling remains necessary for a full photic response in the SCN even after the termination of the photic signal, but that this dependency ends once GRP-dependent signaling is complete.
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, OH 44242, USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Kallingal
authors.forename: Eric M
authors.initials: EM
authors.lastname: Mintz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D008027:Light; D008297:Male; D008845:Microinjections / Q000379:methods; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005765:Gastrointestinal Agents; D016194:Receptors, N-Methyl-D-Aspartate; C056639:2-amino-5-phosphopentanoic acid; D019886:Gastrin-Releasing Peptide; D014633:Valine