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Histamine‐1 receptor is not required as a downstream effector of orexin‐2 receptor in maintenance of basal sleep/wake states
Author(s) -
Hondo M.,
Nagai K.,
Ohno K.,
Kisanuki Y.,
Willie J. T.,
Watanabe T.,
Yanagisawa M.,
Sakurai T.
Publication year - 2010
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2009.02032.x
Subject(s) - orexin , basal (medicine) , histamine , effector , receptor , downstream (manufacturing) , orexin receptor , endocrinology , medicine , microbiology and biotechnology , biology , neuropeptide , engineering , operations management , insulin
Aim: The effect of orexin on wakefulness has been suggested to be largely mediated by activation of histaminergic neurones in the tuberomammillary nucleus (TMN) via orexin receptor‐2 (OX 2 R). However, orexin receptors in other regions of the brain might also play important roles in maintenance of wakefulness. To dissect the role of the histaminergic system as a downstream mediator of the orexin system in the regulation of sleep/wake states without compensation by the orexin receptor‐1 (OX 1 R) mediated pathways, we analysed the phenotype of Histamine‐1 receptor (H 1 R) and OX 1 R double‐deficient ( H 1 R −/− ; OX 1 R −/− ) mice. These mice lack OX 1 R‐mediated pathways in addition to deficiency of H 1 R, which is thought to be the most important system in downstream of OX 2 R. Methods: We used H 1 R deficient ( H 1 R −/− ) mice, H 1 R −/− ; OX 1 R −/− mice, OX 1 R and OX 2 R double‐deficient ( OX 1 R −/− ; OX 2 R −/− ) mice, and wild type controls. Rapid eye movement (REM) sleep, non‐REM (NREM) sleep and awake states were determined by polygraphic electroencephalographic/electromyographic recording. Results: No abnormality in sleep/wake states was observed in H 1 R −/− mice, consistent with previous studies. H 1 R −/− ; OX 1 R −/− mice also showed a sleep/wake phenotype comparable to that of wild type mice, while OX 1 R −/− ; OX 2 R −/− mice showed severe fragmentation of sleep/wake states. Conclusion: Our observations showed that regulation of the sleep/wake states is completely achieved by OX 2 R‐expressing neurones without involving H 1 R‐mediated pathways. The maintenance of basal physiological sleep/wake states is fully achieved without both H 1 and OX 1 receptors. Downstream pathways of OX 2 R other than the histaminergic system might play an important role in the maintenance of sleep/wake states.