| Project/Area Number |
26461730
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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 |
Psychiatric science
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
Akiyoshi Saitoh 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 室長 (00366832)
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| Co-Investigator(Kenkyū-buntansha) |
山田 美佐 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 科研費研究員 (10384182)
関口 正幸 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第四部, 室長 (80260339)
岡 淳一郎 東京理科大学, 薬学部薬学科, 教授 (40134613)
山田 光彦 国立研究開発法人国立精神・神経医療研究センター, 精神保健研究所 精神薬理研究部, 部長 (60240040)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 行動薬理 / 精神薬理 / 行動薬理学 / 精神薬理学 / オピオイドδ受容体 / 情動行動 / 不安様行動 / 内側前頭前野前辺縁皮質領域 / 抗不安様作用 |
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| Outline of Final Research Achievements |
The local co-perfusion of a selective δ opioid receptor (DOR) agonist KNT-127 with a sodium channel activator veratrine in prelimbic medial prefrontal cortex (PL-PFC) diminished the veratrine-induced anxiety-like behaviors and extracellular glutamate levels. Interestingly, KNT-127 diminished a glutamate transporter inhibitor TFB-TBOA-induced anxiety-like behaviors without effect on TFB-TBOA-induced extracellular glutamate levels. These inhibitory effects of KNT-127 were antagonized by the co-perfusion of a DOR antagonist NTI. Based on these results, we suggested that KNT-127 in the PL-PFC reduced anxiety-like behaviors by suppressing the pre/post-synaptically glutamatergic transmission, bidirectionally. We proposed that a DOR agonist KNT-127 that inhibits glutamatergic transmission in the PL-PFC is a possible candidate for a novel anxiolytic.
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