Extended action of MKC-242, a selective 5-HT(1A) receptor agonist, on light-induced Per gene expression in the suprachiasmatic nucleus in mice.
We reported previously that (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole hydrochloride (MKC-242) (3 mg kg(-1), i.p.), a selective 5-HT(1A) receptor agonist, accelerated the re-entrainment of hamster wheel-running rhythms to a new 8 hr delayed or advanced light-dark cycle, and also potentiated the phase advance of the wheel-running rhythm produced by light pulses. The molecular mechanism underlying MKC-242-induced potentiation of this phase shift, however, has not yet been elucidated. We examined the effects of MKC-242 on light-induced mPer1 and mPer2 mRNA expression in the suprachiasmatic nucleus (SCN) of mice. MKC-242 (5 mg kg(-1), i.p.) potentiated light-induced mPer1 and mPer2 expression in the SCN of mice housed in constant darkness for 2 days, when mRNA levels were observed 3 hr after light-exposure. More potentiating action of MKC-242 on mPer2 expression in the SCN was observed in mice housed in constant darkness for 9-10 days. This facilitatory action of MKC-242 on mPer1 expression was antagonized by WAY100635, a selective 5-HT(1A) receptor blocker, indicating that MKC-242 activated 5-HT(1A) receptors. Other drugs such as 8-hydroxy-dipropylaminotetralin (10 mg kg(-1), i.p.), paroxetine (10 mg kg(-1), i.p.), buspirone (10 mg kg(-1), i.p.), and diazepam (10 mg kg(-1), i.p.) did not display a potentiating action on light-induced mPer1 and mPer2 expression in the SCN. In the behavioral experiments, we found that MKC-242 (5 mg kg(-1), i.p.) potentiated light-induced phase delays of free-running rhythm in mice. The present results suggest that prolonged increase of mPer1 or mPer2 expression in the SCN by MKC-242 may be involved in the potentiation of photic entrainment by MKC-242 in mice.
Takahashi
Satomi
S
Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.
Yoshinobu
Yuko
Y
Aida
Reiko
R
Shimomura
Haruka
H
Akiyama
Masashi
M
Moriya
Takahiro
T
Shibata
Shigenobu
S
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm; D003975:Diazepam / Q000494:pharmacology; D004146:Dioxanes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004149:Dioxoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D008027:Light; D008297:Male; D051379:Mice; D009043:Motor Activity; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D017374:Paroxetine / Q000494:pharmacology; D056950:Period Circadian Proteins; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D014157:Transcription Factors
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone; D018797:Cell Cycle Proteins; D003975:Diazepam; D004146:Dioxanes; D004149:Dioxoles; D018757:GABA Modulators; D009687:Nuclear Proteins; D017374:Paroxetine; D056950:Period Circadian Proteins; D010879:Piperazines; D011725:Pyridines; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014157:Transcription Factors; C539022:PER1 protein, human; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C096294:osemozotan