Arousal effect of orexin A depends on activation of the histaminergic system

Zhi Li Huang, Wei Min Qu, Wei Dong Li, Takatoshi Mochizuki, Naomi Eguchi, Takeshi Watanabe, Yoshihiro Urade, Osamu Hayaishi*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

512 被引用数 (Scopus)

抄録

Orexin neurons are exclusively localized in the lateral hypothalamic area and project their fibers to the entire central nervous system, including the histaminergic tuberomammillary nucleus (TMN). Dysfunction of the orexin system results in the sleep disorder narcolepsy, but the role of orexin in physiological sleep-wake regulation and the mechanisms involved remain to be elucidated. Here we provide several lines of evidence that orexin A induces wakefulness by means of the TMN and histamine H1 receptor (H1R). Perfusion of orexin A (5 and 25 pmol/min) for 1 hr into the TMN of rats through a microdialysis probe promptly increased wakefulness for 2 hr after starting the perfusion by 2.5and 4-fold, respectively, concomitant with a reduction in rapid eye movement (REM) and non-REM sleep. Microdialysis studies showed that application of orexin A to the TMN increased histamine release from both the medial preoptic area and the frontal cortex by ≅2-fold over the baseline for 80 to 160 rain in a dose-dependent manner. Furthermore, infusion of orexin A (1.5 pmol/min) for 6 hr into the lateral ventricle of mice produced a significant increase in wakefulness during the 8 hr after starting infusion to the same level as the wakefulness observed during the active period in wild-type mice, but not at all in H1R gene knockout mice. These findings strongly indicate that the arousal effect of orexin A depends on the activation of histaminergic neurotransmission mediated by H1R.

本文言語英語
ページ(範囲)9965-9970
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
98
17
DOI
出版ステータス出版済み - 2001/08/14

ASJC Scopus 主題領域

  • 一般

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