Activation of 5-HT2C receptors acutely induces Per gene expression in the rat suprachiasmatic nucleus at night.
The suprachiasmatic nucleus (SCN) of the hypothalamus receives dense serotonergic projections from the raphe nuclei and this input has been implicated in the modulation of circadian rhythms. In the present study, we investigated the effect of 5-HT2C receptor activation on various clock genes within the suprachiasmatic nucleus, including Per1 and Per2, which have previously been demonstrated as necessary for phase shifts. Rats were exposed to light (400 lx, 15 min), administered 5-HT2C receptor agonists (+/-)-1-(4-iodo-2,5-dimethoxy-phenyl)-2-aminopropane (DOI) (2 mg/kg) or RO 60-0175 (10 mg/kg) or vehicle 4 or 10 h after dark onset (ZT16 and ZT22). The expression of Per1, Per2, Cry1, Clock, Bmal1, Dec1, Dec2 and c-fos was determined 30 and 120 min after treatment in suprachiasmatic nucleus punches by real time reverse transcription-polymerase chain reaction (RT-PCR). Light exposure induced a 7-fold increase in c-fos expression within 30 min of treatment at both ZT16 and ZT22. Per1 expression was increased 2-fold following light exposure at ZT22, whereas treatment at ZT16 had no significant effect. Per2 expression was significantly induced following light at ZT16, but was not affected at ZT22. RO 60-0175 or DOI administration induced a 5-fold change in c-fos expression at ZT16 and a 3-fold change at ZT22 within 30 min of treatment. The drug increased both Per1 and Per2 expression at ZT16, but had no effect at ZT22. These results provide evidence for 5-HT2C receptors being involved in the modulation of circadian rhythms during early night.
Varcoe
Tamara J
TJ
Department of Obstetrics and Gynaecology, University of Adelaide Medical School, Frome Road, Adelaide 5005, South Australia, Australia. tamara.varcoe@adelaide.edu.au
Kennaway
David J
DJ
Voultsios
Athena
A
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000235:genetics*; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D003624:Darkness; D004525:Efferent Pathways / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D010775:Photic Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists; D014157:Transcription Factors