The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Arousal effect of orexin A depends on activation of the histaminergic system
Open accessAbstract
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 H 1 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 2.5- and 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 min 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.
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Cited by
Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565
Control of sleep and wakefulness
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General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
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The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness
Sakurai, T. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2092 · Cited by 1,276
The role of histamine and the tuberomamillary nucleus in the nervous system
Haas, H., & Panula, P. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1034 · Cited by 929
Metadata
- Authors
- Huang, Z.-L., Qu, W.-M., Li, W.-D., Mochizuki, T., Eguchi, N., Watanabe, T., Urade, Y., & Hayaishi, O.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-08-07
- Volume
- 98
- Issue
- 17
- Pages
- 9965-9970
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2042040860
- Cited by
- 553
- References
- 49
- FWCI
- 13.03
- Type
- journal article
- Language
- en
- Open access
- green
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- Huang, Z.-L., Qu, W.-M., Li, W.-D., Mochizuki, T., Eguchi, N., Watanabe, T., Urade, Y., & Hayaishi, O. (2001). Arousal effect of orexin A depends on activation of the histaminergic system. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.181330998
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