| Project/Area Number |
17390423
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Hirosaki University |
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Principal Investigator |
HIROTA Kazuyoshi Hirosaki University, Hirosaki University, Graduate School of Medicine, Professor (20238413)
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| Co-Investigator(Kenkyū-buntansha) |
KUDO Mihoko Hirosaki University, Graduate School of Medicine, Assistant Professor (30003411)
KUSHIKATA Tetsuya Hirosaki University, University Hospital, Lecturer (80250603)
KUDO Tsuyoshi Hirosaki University, Graduate School of Medicine, Assistant Professor (70003407)
YOSHIDA Hitoshi Hirosaki University, University Hospital, Assistant Professor (00374843)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥10,440,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥840,000)
Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | orexin / noradrenaline / rat / microdialysis / cerebrocortical slice / ノルエピネフリン / 大脳皮質 / 電撃痙攣療法 / α受容体作リガンド / ベンゾジアゼピン / 神経組織 / 吸入麻酔薬 / 静脈麻酔薬 |
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| Research Abstract |
The present data support our hypothesis that both inhibition and overexcitation of noradrenergic neurons by GABA-type and NMDA-type of anesthetics, respectively, contribute to the mechanism of general anesthesia (=loss of consciousness). Orexin increases noradrenergic neuronal activity but the increase is saturable around 250% of the basal, whose level of noradrenergic neuronal activity may induce the maximal wakefulness in our hypothesis. In addition, the present data indicates that orexinergic neurons could be a target for both GABA-type and NMDA-type of anesthetic agents as orexin decreased both barbiturates (GABA-type) and ketamine (NMDA-type)-produced anesthesia time. Orexin also antagonized thiopental-induced inhibition of and ketamine-caused overexcitatio of noradrenergic activity. Yohimbin 10 mg/kg ip increased cerebral noradrenaline release to ~500% of the basal, and this increase prolonged GABA-type anesthetic propofol-produced anesthesia time. This means that overexcitation of noradrenergic neuronal activity could also enhance GABA-type anesthetics-produced anesthesia. It is known that DSP-4 lesions locus coeruleus-originated noradrenergic neurons. The lesion increased thiopental anesthesia time and decreased ketamine anesthesia time. In addition, there were significant correlations between cerebral noradrenaline contents and increase in thiopental anesthesia time or decrease in ketamine anesthesia time. Therefore, we proved our hypothesis that both inhibition and overexcitation of noradrenergic neurons contribute to loss of consciousness.
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