| Project/Area Number |
16K08539
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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 |
Environmental physiology(including physical medicine and nutritional physiology)
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Uchiyama Nahoko 国立医薬品食品衛生研究所, 生薬部, 室長 (60392297)
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| Co-Investigator(Kenkyū-buntansha) |
有竹 浩介 第一薬科大学, 薬学部, 教授 (70390804)
マリシェフサカヤ オリガ 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (20739429)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | カンナビノイド / 脳波 / 多変量解析 / 睡眠 / 痙攣 / 覚醒 |
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| Outline of Final Research Achievements |
An intraperitoneal administration of Δ9-THC or JWH-018 triggered electrographic seizures in mice, recorded by EEG and videography. Administration of JWH-018 increased seizure spikes dose-dependently. Pretreatment of mice with AM-251, a cannabinoid receptor 1 (CB1R)-selective antagonist, completely prevented cannabinoid-induced seizures. The results clearly show that the epileptogenic properties of cannabinoids are mediated via CB1R. Additionally, CB1RKO mice show no electrographic or behavior seizures after JWH-018 administration confirming again the mediation of seizure phenomenon by CB1R.
Multivariate analysis of EEG in mice treated with JWH-018 and cannabocyclohexanol was performed. As a result of discriminant analysis, both drugs were divided into a drug administration group and a solvent administration group on the Score plot. Moreover, it was clearly shown that the EEG frequency contributing to the drug administration group was 2.5 to 5.5 Hz (delta wave) for both drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
本成果は，カンナビノイドの睡眠調節に関する作用の解明に加えて，カンナビノイドの既知の中枢作用にも何らかの関与が見いだされる可能性もある．多変量解析を用いた脳波解析は，睡眠・覚醒を含めた様々な脳波パターンを識別するための判断ツールとして有用であると考えられる．従って，不眠などの睡眠障害の原因解明や，ひいては睡眠に関する新たな治療薬の開発にも繋がることが期待できる．
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