• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



Sleep and Biological Rhythms

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Effects of 5-HT1A receptor agonist on the narcoleptic like effects in orexin knockout mice

  • P2-212
  • 鵜澤 直生 / Naoki Uzawa:1 森 友久 / Tomohisa Mori:1 岩瀬 祥之 / Yoshiyuki Iwase:1 平山 重人 / Shigeto Hirayama:1 増川 太輝 / Daiki Masukawa:1 ラハマディ マハルディアン / Mahardian Rahmadi:1 外園 真由奈 / Mayuna Hokazono:1 芝崎 真裕 / Masahiro Shibasaki:1 鈴木 勉 / Tsutomu Suzuki:1 
  • 1:星薬大・薬品毒性 / Dept. of Toxicol, Hoshi Univ of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan 

Orexin knockout (KO) mice exhibit a phenotype that is similar to human narcolepsy. Orexin-containing neurons project to all brain regions, such as raphe nuclei, 5-HT nucleus, and are thought to involve in sleep and arousal by interaction with monoaminergic neurons. It has been reported that dysfunction of serotoninergic neurons were changed in orexin KO mice, and these studies suggest that serotonin-related compounds are useful for narcolepsy. Psychostimulants and monoamine uptake inhibitors, which increase the monoaminergic tone, have been used for treatment of human narcolepsy and cataplexy associated the narcolepsy. However, pathophysiological feature of orexin KO mice regarding narcoleptic-like sleep disorder and how psychostimulants and monoamine-related compounds affect narcoleptic-like sleep disorder in orexin KO mice have not been cleared yet. Therefore, the present study was designed to investigate the changes of monoaminergic neurons in orexin KO mice, and therapeutic agents for narcoleptic like effects in orexin KO mice. In the present study, orexin KO mice showed the significant decrease in wakefulness and locomotor activity in the dark phase as compared with wild type mice. Psychostimulants, such as methamphetamine, methylphenidate and 3,4-methylenedioxymethamphetamine, the 5-HT1A-receptor agonist 8-OH-DPAT and 5-HT2-receptor agonist DOI increased locomotor activity in orexin KO mice at dark periods, indicating the validity of these drugs for treatment of human narcolepsy. Interestingly, 5-HT1A-receptor mRNA levels, but not mRNA levels of 5-HT2 and dopamine receptors, in the prefrontal cortex were significantly decreased in orexin KO mice. Furthermore, significant decrease in wakefulness (accompanied by significant increase in time of REM sleep) in orexin KO mice was completely normalized by administration of the 8-OH-DPAT. These results suggest that dysfunction of 5-HTnergic system is involved in the narcoleptic-like sleep dysfunction of orexin KO mice, and 5-HT1A receptor agonist may have sleep normalizing effects in the orexin deficient-induced sleep disorders.

Copyright © Neuroscience2014. All Right Reserved.