Short-term constant light potentiation of large-magnitude circadian phase shifts induced by 8-OH-DPAT: effects on serotonin receptors and gene expression in the hamster suprachiasmatic nucleus.
Nonphotic phase-shifting of mammalian circadian rhythms is thought to be mediated in part by serotonin (5-HT) acting in the suprachiasmatic nucleus (SCN) circadian clock. Previously we showed that brief (1-3 days) exposure to constant light (LL) greatly potentiates nonphotic phase-shifting induced by the 5-HT agonist, (+/-)2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT). Here we investigated potential mechanisms for this action of LL, including 5-HT receptor upregulation and SCN clock gene and neuropeptide gene expression. Autoradiographic analysis of ritanserin inhibition of [3H]8-OH-DPAT binding indicated that LL (approximately 2 days) did not affect 5-HT7 receptor binding in the SCN or dorsal raphe. Measurement of 5-HT1A autoreceptors in the median raphe and 5-HT1B receptors in the SCN also showed no effect of LL. In experiment 2, hamsters held under a 14-h light : 10-h dark photocycle (LD) or exposed to LL for approximately 2 days received an intraperitoneal injection of 8-OH-DPAT or vehicle at zeitgeber time (ZT) 6 or 0 and were killed after 2 h of dark exposure. 8-OH-DPAT suppressed SCN Per1 and Per2 mRNAs at both ZTs, as assessed by in situ hybridization. Per1 mRNA was also suppressed by LL alone. In addition, in situ hybridization of arginine vasopressin (AVP) mRNA and vasoactive intestinal polypeptide mRNA showed that LL significantly suppressed the former but not the latter. The LL-induced suppression of SCN Per1 mRNA and AVP mRNA may be involved in LL-induced potentiation of pacemaker resetting, especially as these data provide additional evidence that LL suppresses circadian pacemaker amplitude, thus rendering the clock more susceptible to phase-shifting stimuli.
Duncan
Marilyn J
MJ
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. mjdunc0@uky.edu
Franklin
Kathleen M
KM
Davis
Verda A
VA
Grossman
Gregory H
GH
Knoch
Megan E
ME
Glass
J David
JD
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D006224:Cricetinae; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D017403:In Situ Hybridization / Q000379:methods; D008027:Light; D008297:Male; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009687:Nuclear Proteins / Q000235:genetics; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D014157:Transcription Factors / Q000235:genetics; D014316:Tritium / Q000493:pharmacokinetics; D014660:Vasoactive Intestinal Peptide / Q000235:genetics
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014157:Transcription Factors; D014316:Tritium; D001127:Arginine Vasopressin; D014660:Vasoactive Intestinal Peptide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin