| Project/Area Number |
11670934
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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, Assistant Professor, 生体材料工学研究所, 助手 (70173656)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Orexin / Narcolepsy / non-REM sleep / REM sleep / Sleep-waking system / Dopamine / 覚醒維持機構 / 睡眠・覚醒調節 |
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| Research Abstract |
Orexins A and B are novel neuropeptides which are known to regulate the appetite system. Recent studies showed that canine narcolepsy is caused by deficit in the orexin-2 receptor gene, and that prepro-orexin knock-out mice exhibited similar behavior to human and canine narcoleptics. Orexin-containing neurons are localized in the lateral hypothalamic area and densely project to the noradrenergic locus coeruleus, dopaminergic ventral tegmental area, serotonergic dorsal raphe nuclei and histaminergic tuberomammillary nucleus. Intracerebroventricular (icv) infusion of orexins A and B induced significant arousal effect in the freely behaving normal-male Sprague-Dawley rats. Cortical EEG and neck EMG were monitored for three consecutive days , during continuous icv saline infusion at a rate of 10 μl/h. For 5-h diurnal period, either orexin A (0.1-10 nmol) or B ( 1-40 nmol) replaced. the icv infusion of saline. Orexin A at the dose of 10 nmol markedly increased the amount of wakefulness by 228.6% (p<0.01) whereas orexin B at the same dose caused an increase of 99.8% (p<0.01) over the baseline value. Both orexins caused dose-dependent increases in wakefulness. The enhancement of arousal was due to a marked reduction in sleep. The data indicate that orexin A is more effective in causing a state of arousal than orexin B at the same dose. Since orexin A has equal affinity for both the orexin-1 and orexin-2 receptors but orexin B only shows affinity for the orexin-2 receptor, thus exogenous administration of orexin A might be more effective in enhancing a state of arousal than orexin B.In conclusion, the results suggest that orexins A and B may play important physiological roles in the regulation of sleep-waking cycle through both the orexin-1 and orexin-2 receptor sites.
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