Activation of 5-HT2C receptors acutely induces Per1 gene expression in the rat SCN in vitro.
The suprachiasmatic nucleus of the hypothalamus receives dense serotonergic projections from the raphe nuclei. This input may be involved in the transmission of photic information with activation of 5-HT receptors at night having a photo-mimetic effect. 5-HT2C receptors have been implicated in this role, with 5-HT2C receptor agonist administration at night resulting in the induction of cFOS protein, and a phase delay of melatonin metabolite excretion rhythms in a manner similar to light. To investigate the site of action of 5-HT2C receptor agonists, rat SCN explants were isolated in culture, allowing exposure of agonists to denervated tissue. Any response could then be attributed to the actions of the 5-HT2C receptor agonist on cells within the SCN, rather than at other distant sites or on pre-synaptic receptors. Rat SCN tissue was microdissected and prepared in tissue culture conditions. The acute effect of the 5-HT2A/2C receptor agonist DOI and glutamate administration at various circadian times on c-fos and Per1 expressions was assessed. Glutamate induced the expression of c-fos at CT6, CT16 and CT22, but induced Per1 expression at CT16 only. DOI altered c-fos expression at all times examined with an increase at CT6 and CT22, and a repression at CT16. However, DOI significantly increased Per1 expression when applied at CT16, but had no effect at either CT22 or CT6. This response was similar to that previously observed in vivo. This provides support for the hypothesis that the actions of 5-HT2C receptor agonists are on cells located within the SCN.
Varcoe
Tamara J
TJ
Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, Australia. tamara.varcoe@adelaide.edu.au
Kennaway
David J
DJ
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D055537:Light Signal Transduction / Q000187:drug effects / Q000235:genetics; D008297:Male; D008550:Melatonin / Q000378:metabolism; D009924:Organ Culture Techniques; D056950:Period Circadian Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*
D018797:Cell Cycle Proteins; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D016760:Proto-Oncogene Proteins c-fos; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018698:Glutamic Acid; D008550:Melatonin