title: Potentiating action of MKC-242, a selective 5-HT1A receptor agonist, on the photic entrainment of the circadian activity rhythm in hamsters.
abstract: Serotonergic projections from the midbrain raphe nuclei to the suprachiasmatic nuclei (SCN) are known to regulate the photic entrainment of circadian clocks. However, it is not known which 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the circadian regulation. In order to verify the role of 5-HT1A receptors, we examined the effects of 5-¿3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]-propoxy¿-1,3-b enzodioxole HCl (MKC-242), a selective 5-HT1A receptor agonist, on photic entrainment of wheel-running circadian rhythms of hamsters. MKC-242 (3 mg kg(-1), i.p.) significantly accelerated the re-entrainment of wheel-running rhythms to a new 8 h delayed or advanced light-dark cycle. MKC-242 (3 mg kg(-1), i.p.) also potentiated the phase advance of the wheel-running rhythm produced by low (5 lux) or high (60 lux) intensity light pulses. In contrast, 8-hydroxydipropylaminotetralin (8-OH-DPAT)(5 mg kg(-1), i.p.), a well known 5-HT1A/5-HT7 receptor agonist, only suppressed low intensity (5 lux) light-induced phase advances. The potentiating actions of MKC-242 on light pulse-induced phase advances were observed even when injected 20 or 60 min after the light exposure. The potentiating action of MKC-242 was antagonized by WAY100635, a selective 5-HT1A receptor blocker, but not by ritanserin, a 5-HT2/5-HT7 receptor blocker, indicating that MKC-242 is activating 5-HT1A receptors. Light pulse-induced c-fos expression in the SCN and the intergeniculate leaflet (IGL) were unaffected by MKC-242 (3 mg kg(-1), i.p.). HPLC analysis demonstrated that MKC-242 (3 mg kg(-1), i.p.) decreased the 5-HIAA content in the SCN. The present results suggest that presynaptic 5-HT1A receptor activation may be involved in the potentiation of photic entrainment by MKC-242 in hamsters.
authors.affiliation: Advanced Research Center for Human Sciences, School of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Moriya
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshinobu
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Yokota
authors.forename: M
authors.initials: M
authors.lastname: Akiyama
authors.forename: S
authors.initials: S
authors.lastname: Shibata
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D004146:Dioxanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D005830:Geniculate Ganglion / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008027:Light; D008297:Male; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010775:Photic Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure
chemical_list: D004146:Dioxanes; D004149:Dioxoles; D016760:Proto-Oncogene Proteins c-fos; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C096294:osemozotan