| Project/Area Number |
14570912
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
HONDA Kazuki Tokyo Medical and Dental University, Institute of Biomaterials and Bioengineering, Associate Professor, 生体材料工学研究所, 助教授 (70173656)
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| Co-Investigator(Kenkyū-buntansha) |
木村 昌由美 東京医科歯科大学, 生体材料工学研究所, 助手 (40216859)
IWASAKI Yasuhiko Tokyo Medical and Dental University, Institute of Biomaterials and Bioengineering, Associate Professor, 生体材料工学研究所, 助教授 (90280990)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Orexin / Histamine / Narcolepsy / Sleep / Pyrilamine / 睡眠覚醒 / ラット / 第三脳室内連続注入 / 脳波 |
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| Research Abstract |
Orexins A and B are novel neuropeptides involved in the regulation of feeding and arousal state. Orexin-containing neurons are localized in the lateral hypothalamic area and densely project to the locus coeruleus, ventral tegmental area, dorsal raphe nuclei and tuberomammillary nucleus (TMN). Previously, we reported that intracerebroventricular (icy) infusion into the third ventricle of both orexins A and B induced arousal effect in the rats. Recently, we found direct synaptic connectivity between orexin nerve terminals and histaminergic neurons in the TMN where the OX2R is abundantly expressed. Hence, orexin-induced arousal state seems to be regulated via histaminergic neurons in the TMN. In this study, we investigate the effects of icy infusion of pyrilamine (an Hi receptor antagonist) on orexin-induced wakefulness in rats. Cortical FEG and neck EMG were monitored for three consecutive days, during continuous icy saline infusion at a rate of 10 rd/h. For diurnal period, orexin A (1 n
… More
mol/20 ul saline) and pyrilamine (25 or 75 ug/25 ul saline) replaced the icy infusion of saline. Pyrilamine administration was started 30 mm before orexin A infusion. The icy infusion of orexin A for a 2-h period markedly increased the amount of wakefulness by 340.0 % (p<0.05) over the baseline value. Pyrilamine decreased orexin A-induced wakefulness by 85 % (p<0.05) and 58 % (p<0.05), at 25 and 75 ug/2.5-h period, respectively. Pyrilamine caused a dose-dependent decrease in the orexin A-induced arousal effect. Orexin A-induced suppression of non-REM sleep was dose-dependently reversed by pyrilamine treatment. Although pyrilamine treatment alone (75 ug) slightly decreased REM sleep, no significant difference was observed. Pyrilamine, an Hi receptor antagonist, significantly inhibited the effects of orexin A-induced wakefulness. Since orexin neurons densely innervate TMN where OX_2R is highly expressed, orexin neurons might regulate the arousal state through modulating the activity of histaminergic neurons in the TMN. Less
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