| Project/Area Number |
16590442
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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 |
Applied pharmacology
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| Research Institution | Meijo University |
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Principal Investigator |
HIRAMATSU Masayuki Meijo University, Faculty of Pharmacy, ASSOCIATE PROFESSOR, 薬学部, 助教授 (10189863)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | κ-opioid / dynorphin A / nociceptin / restraint water-immersion stress / cholinergic nerve / β-amyloid peptide / learning and memory / catechin / dynorphin A / ORL1受容体 / mRNA発現量 / ダイノルフィンA / ノシセプチン / 脳内微量透析法 / アセチルコリン |
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| Research Abstract |
We have reported that kappa-opioid receptor agonist such as dynorphin A improved learning and memory impairment in several animal models with cholinergic dysfunction. Nociceptin is an endogenous ligand for the opioid receptor-like 1 (ORL1) receptor and has some structural homology with the dynorphin A. We have suggested that the ameliorating effect of low doses nociceptin in learning and/or memory impairment may not be mediated by ORL1 receptor. In the hippocampus of ORL1 receptor knockout mouse, expression of kappa_1 opioid receptor mRNA decreased, while mRNA expression of dynorphin and nociceptin precursor protein significantly increased. These changes were presented in beta-amyloid peptide (25-35)-treated mice. The mRNA expression levels of dynorphin precursor protein in the hippocampus 1 week after beta-amyloid peptide (25-35) administration significantly decreased in ORL1 receptor knockout mouse. We used restraint water-immersion stress model and lipopolysaccharide (LPS) to induce delayed and progressive learning and memory impairment to test the effect of dynorphin A and nociceptin. After water-immersion stress, short-term memory was impaired 5 days after stress exposure and the passive avoidance learning was impaired 7 days after stress exposure. These impairments were significantly ameliorated by the antidepressant, desipramine and the acetylcholine esterase inhibitor, tacrine. In addition, they were also ameliorated by antioxidants such as catechin by repeated administration. Further, delayed impairment of learning and memory induced by LPS was also ameliorated by repeated administration of catechin. We need to elucidate the mechanisms of dynorphin A related peptides in these animal models.
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