Effects of D-serine on tolerance to the antinociceptive effects of morphine
| Project/Area Number |
26462385
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Anesthesiology
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| Research Institution | Tokai University |
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Principal Investigator |
ITO Kenji 東海大学, 医学部, 准教授 (10317779)
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| Co-Investigator(Kenkyū-buntansha) |
吉川 正信 東海大学, 医学部, 准教授 (90276791)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | モルヒネ / 鎮痛耐性形成 / Dセリン / NMDA受容体 / dynorphin / 鎮痛耐性 / モルヒネ慢性投与 |
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| Outline of Final Research Achievements |
Chronic morohine administration induced mRNA expression of serine racemase in all brain regions and spinal cord and that of D-amino acid oxidase in forebrain of rats. Dynorphin A and its derived peptides interact with opioid and glutamate receptors at their N- and C-terminals, respectively. Pretreatment with peptidase inhibitors augmented Dyn A (1-17) or (1-13)-induced antinociception by approximately 50- or 30-fold with no sign of allodynia when administered intrathecally at low doses. Pretreatment with peptidase inhibitors induced neuropathy. These findings showed that intrathecal administration of low-dose Dyn A (1-17) or Dyn A (1-13) increased antinociception under pretreatment with ACP, but without signs of allodynia in rat. These results indicated that administration of chronic morphine increased dynorphin A (1-17), and then induced nociception through NMDA receptors.
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Report
(4 results)
Research Products
(2 results)
