Altered sleep-wake characteristics and lack of arousal response to H3 receptor antagonist in histamine H1 receptor knockout mice

Proceedings of the National Academy of Sciences of the United States of America
Zhi-Li HuangO Hayaishi

Abstract

Histaminergic neurons play an important role in the regulation of sleep-wake behavior through histamine H(1) receptors (H(1)R). Blockade of the histamine H(3) receptor (H(3)R) is proposed to induce wakefulness by regulating the release of various wake-related transmitters, not only histamine. In the present study, we characterized sleep-wake cycles of H(1)R knockout (KO) mice and their arousal responses to an H(3)R antagonist. Under baseline conditions, H(1)R KO mice showed sleep-wake cycles essentially identical to those of WT mice but with fewer incidents of brief awakening (<16-sec epoch), prolonged durations of non-rapid eye movement (NREM) sleep episodes, a decreased number of state transitions between NREM sleep and wakefulness, and a shorter latency for initiating NREM sleep after an i.p. injection of saline. The H(1)R antagonist pyrilamine mimicked these effects in WT mice. When an H(3)R antagonist, ciproxifan, was administered i.p., wakefulness increased in WT mice in a dose-dependent manner but did not increase at all in H(1)R KO mice. In vivo microdialysis revealed that the i.p. application of ciproxifan increased histamine release from the frontal cortex in both genotypes of mice. These results indicate that H(1)R i...Continue Reading

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Citations

Sep 15, 2012·Neurogenetics·Jessica M Kelly, Matt T Bianchi
Dec 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yo OishiOsamu Hayaishi
Apr 19, 2008·Cold Spring Harbor Symposia on Quantitative Biology·M Tafti, P Franken
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Dec 17, 2014·Pharmacology, Biochemistry, and Behavior·Yi-Qun WangZhi-Li Huang
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