| Co-Investigator(Kenkyū-buntansha) |
KUDO Mihoko Hirosaki University, School of Medicine, Instructor, 医学部, 助手 (30003411)
KUSHIKATA Tetsuya Hirosaki University, University Hospital, Instructor, 医学部附属病院, 助手 (80250603)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥11,600,000 (Direct Cost: ¥11,600,000)
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| Research Abstract |
In Vitro
1.Effects of orexin(OX) on neurotransmitter releases from the cerebral cortex.
Both OXA and B concentration-dependently increased only norepinephrine(NE) release but did not other neurotransmitters such as dopamine, glutamate, 5HT and histamine. Therefore, OX may selectively increase NE release from rat cerebral cortex.
2.Effects of OX_1 antagonist on OXA and B-evoked NE 放出 release.
As SB334867,an OX1 antagonist, almost fully inhibited OXs-evoked NE release, the release may be mediated via OX_1 receptors.
3.Effects of anesthetics on OX-evoked NE release.
1)GABA-type anesthetics : Clinically relevant concentrations of anesthetic barbiturates significantly inhibited OX-evoked NE release. However, inhibitory effects of thiopental on the OX-evoked release was not reversed by bicuculline, a GABA_A receptor antagonist. In addition, muscimol, a GABA_A receptor agonist, did not inhibit the OX-evoked release. Therefore, anesthetic barbiturates may inhibit OXergic neurons not via GABA_A receptors.
3)NMDA-type anesthetics : Ketamine significantly inhibited OXA-evoked NE release hi its clinical range. In addition, MK801,a NMDA receptor antagonist, also inhibited the release. Therefore, inhibitory effects of ketamine may be mediated via NMDA receptors.
In Vivo
1.Effects of icv OX on cerebrocortical NE release.
Iev OXA dose-dependently increased cerebrocortical NE release, which was confirmed with microdialysis method. The degree of increases in NE release by icv OXA was similar to that of OXA-evoked NE release from in vitro cerebrocortical slices.
2.Influence of icv OX on anesthesia time.
1)GABA-type anesthetics : Icv OXs significantly decreased barbiturate-anesthesia time. In contrast, OX1 antagonist increased the time.
2)NMDA-type anesthetics : Icv OXA significantly inhibited ketamine-anesthesia time. This inhibition was antagonized by OX1 antagonist.
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