| Project/Area Number |
11672197
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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 |
Biological pharmacy
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| Research Institution | Meijo University |
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Principal Investigator |
UKAI Makoto Meijo University, Faculty of Pharmacy, Professor, 薬学部, 教授 (80131209)
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| Co-Investigator(Kenkyū-buntansha) |
KANEMATSU Ken Meijo University, Research Institute, Director, 総合研究所, 所長 (70023041)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Endomorphin / Opioid / Opioid receptor antagonist / Anti-dementia drug / Short-term memory / Long-term memory / Neuropeptide / Dementia / オピオイド受容体拮抗薬 / ドパミン受容体 / 受動的回避学習 / 生理活性ペプチド / 自発的交替行動 |
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| Research Abstract |
The effects of the μ-opioid receptor agonists endomorphin-1 and -2 on short- and long-term memory were examined. In addition, the present study was designed to find novel therapeutic drugs for dementia. The μ-opioid receptor antagonist β-funaltrexamine significantly antagonized the endomorphins-induced disturbance of short- and long-term memory. Although the disturbance of short-term memory with endomorphm-1 was significantly improved by the μ1-opioid receptor antagonist naloxonazine, such drug was without any significant effects on the endomorphin-2-induced disturbance of short-term memory. Naloxonazine and the cholmesterase inhibit or physostigmine ameliorated the disturbance of long-term memory. The dopamine D2 receptor agonist RU24213 did not significantly influence the disturbance of short- and long-term memory induced by endomorpnms, the dopamine D2 receptor antagonist (-)-sulpiride significantly antagonized the endomorphins-induced disturbance of short- and long-term memory. From the above results, μ1-opioid receptor, dopamine D2 receptor and cholinergic neurotransmission play a major role in the memory disturbance with endomorpnins. Furthermore, it is possible that μ1-opioid receptor antagonists are useful as novel anti-dementia drugs.
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