Investigation of the interaction between dopamine and noradrenaline signaling in the hippocampus to develop novel treatment of depression
| Project/Area Number |
18K07614
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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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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西 昭徳 久留米大学, 医学部, 教授 (50228144)
外角 直樹 久留米大学, 医学部, 講師 (60368884)
黒岩 真帆美 久留米大学, 医学部, 助教 (20585690)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | うつ病 / ドパミン / 海馬 / 歯状回 / 抗うつ薬 / ノルアドレナリン / 青斑核 |
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| Outline of Final Research Achievements |
We have previously reported that stimulation of D1 receptors in the dentate gyrus enhances the antidepressant actions of a selective serotonin reuptake inhibitor, fluoxetine. However, the detailed mechanism remains to be elucidated. In the present study, we showed that antidepressant effects were obtained by activating the granule cells with high Drd1 promoter activity activity in the dentate gyrus. In addition, we showed that p11 in the ventral tegmental area dopaminergic neurons or nucleus accumbens noradrenergic neurons projecting to the dentate gyrus plays an important role in the stress response and the expression of antidepressant effects.
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| Academic Significance and Societal Importance of the Research Achievements |
うつ病の約３割は既存の治療薬が治療効果を示さない治療抵抗性うつ病とされており、有効性・安全性を向上させた治療薬の開発が望まれている。歯状回に焦点を当てたうつ病に関する研究は、神経新生に焦点を当てたものが中心であるが、この仮説では説明つかない現象も報告されており、未解明なメカニズムの存在が考えられる。歯状回ドパミンD1受容体シグナル活性化による治療効果の増強は、我々が初めて発見した現象であり、抗うつ効果の治療効果発現の中核をなすメカニズムの解明につながることが期待される。また、治療抵抗性うつ病の新たな治療法開発への寄与が期待される。
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Report
(4 results)
Research Products
(6 results)
