| Project/Area Number |
17K15884
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Legal medicine
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| Research Institution | Fujita Health University |
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Principal Investigator |
Ochi Hiroshi 藤田医科大学, 医学部, 助教 (70527704)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 内因性カンナビノイド / ドーパミン / PC12 / 内因性カンナビノイドシステム / ドーパミンシグナリング / 薬物依存 / 脳内報酬系 |
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| Outline of Final Research Achievements |
In this study, we investigated the effect of endocannabinoid 2-AG on dopamine release. We used differentiated-PC12 cells with nerve growth factor as model of dopaminergic neuron. We observed up-regulation of expression of cannabinoid receptor CB1 in these cells. The dopamine release from these cells and increase in intracellular calcium were promoted with hexanal treatment. These promoted dopamine release and elevation of intracellular calcium were significantly suppressed with 2-AG co-treatment.
Generally, it is known that release of neurotransmitters from pre-synapse terminal is caused by the elevation of intracellular calcium. Because Gi protein is coupled with cannabinoid receptor, intracellular calcium is suppressed by activation of cannabinoid receptor. Therefore, it was suggested that suppression of dopamine release is attributed to inhibitory mechanism of intracellular calcium dynamics via activation of cannabinoid receptor by 2-AG.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、内因性カンナビノイドシステムの作用により細胞内カルシウムイオン濃度の上昇を抑制することで、ドーパミン神経モデル細胞からのドーパミン放出が抑制されることが明らかとなった。
ドーパミンが深く関与する中枢神経系機能の一つに脳内報酬系がある。通常、脳内報酬系は欲求が満たされた場合に活性化され、その個体に快の感覚を与える神経系であるが、様々な依存性薬物によっても直接的に刺激されることが知られている。この様な異常な脳内報酬系機能の亢進に対し、内因性カンナビノイドシステムの活性化を介してドーパミンシグナリングを制御することで、依存性薬物の作用だけでなく依存形成を抑制できる可能性が示された。
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