Drug discovery research targeting the novel regulation of prefrontal dopaminergic system by the functional interaction between the sigma1 and serotonin1A receptors
| Project/Area Number |
16K08268
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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 |
Pharmacology in pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
AGO Yukio 大阪大学, 薬学研究科, 准教授 (50403027)
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| Co-Investigator(Kenkyū-buntansha) |
田熊 一敞 大阪大学, 歯学研究科, 教授 (90289025)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | シグマ1受容体 / 5-HT1A受容体 / GABAA受容体 / 相互作用 / ドパミン / 大脳皮質前頭前野 / 抗うつ作用 / 抗不安作用 / σ1受容体 / 5-HT1A 受容体 / SH-SY5Y細胞 / PC12細胞 / 細胞内カルシウム / c-Fos / 腹側被蓋野 / 雌選択性試験 / 抗うつ薬 / アンヘドニア / 前頭葉 |
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| Outline of Final Research Achievements |
This study demonstrates that the functional interaction between the 5-HT1A and sigma1 receptors activates prefrontal dopaminergic system under the conditions of decreased brain GABAA receptor function and the neurochemical effect is linked to the anxiolytic- and antidepressant-like effects. GABAergic deficits cause behavioral and endocrine abnormalities that are associated with psychiatric disorders such as anxiety, depression and schizophrenia. Although the exact mechanisms for the interactions among the 5-HT1A, sigma1 and GABAA receptors are unknown, these receptors are potential targets for the treatment of psychiatric disorders.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は，神経ステロイドの干渉を抑制することで，大脳皮質ドパミン神経機能調節におけるσ1受容体－5-HT1A受容体間の相互作用の存在を見出した．またこの作用には，GABAA受容体の機能変化が密接に関わっていることを明らかにした．本研究の成果は，血中神経ステロイド濃度に応じた抗うつ薬の使い分けや薬剤選択に資する神経化学的基盤を示すものであり，また，神経ステロイドあるいはGABAA受容体機能低下に基づくうつ／不安症状に対して，σ1受容体－5-HT1A受容体の機能的相互作用による前頭葉ドパミン神経の活性化が有効であるといった臨床薬学的・薬物治療学的意義を有するものである．
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] mS-11, a mimetic of the mSin3-binding helix in NRSF, ameliorates social interaction deficits in a prenatal valproic acid-induced autism mouse model.2019
Author(s)
Kawase H, Ago Y, Naito M, Higuchi M, Hara Y, Hasebe S, Tsukada S, Kasai A, Nakazawa T, Mishina T, Kouji H, Takuma K, Hashimoto H.
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Journal Title
Pharmacol Biochem Behav.
Volume: 176
Pages: 1-5
DOI
Related Report
Peer Reviewed / Open Access
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