Verification of the importance of central FFAR1 system in nociceptive and emotional behaviors in mice
| Project/Area Number |
16K10792
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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 |
Neurosurgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
OYOSHI Tatsuki 鹿児島大学, 医歯学域附属病院, 講師 (80315407)
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| Co-Investigator(Kenkyū-buntansha) |
有田 和徳 鹿児島大学, 医歯学総合研究科, 客員研究員 (90212646)
宮田 篤郎 鹿児島大学, 医歯学域医学系, 教授 (60183969)
栗原 崇 鹿児島大学, 医歯学域医学系, 准教授 (60282745)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | FFAR1 / GPR40 / コカイン / 不安様行動 / セロトニン / in vivo マイクロダイアリシス法 / うつ病 / 炎症性疼痛 / 神経障害性疼痛 / FFAR１ / 内因性疼痛抑制機構 / 脳内モノアミン系 / 疼痛・情動行動 |
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| Outline of Final Research Achievements |
The free fatty acid receptor 1 (FFAR1) is suggested to function as a G protein-coupled receptor for medium- to long-chain FFAs. Since the role of central FFAR1 has been largely unclarified, we examined the functional role of FFAR1 in the control of striatal monoamines release and cocaine-induced locomotor activity in this study.
Acute administration of cocaine enhanced locomotor activity in both FFAR1 wild-type (+/+) and knockout (-/-) mice, but the magnitude of enhancement was significantly reduced in -/- mice. Microdialysis studies revealed that the basal level of dopamine was significantly elevated, while the serotonin (5-HT) level was tended to be reduced in -/- mice. Moreover, local application of a FFAR1 agonist, GW9508, markedly augmented the 5-HT release in +/+ mice, but the enhanced release was lost in -/- mice. These results suggest that FFAR1 has a facilitatory role in striatal 5-HT release, which might potentiate cocaine-induced locomotor activity.
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| Academic Significance and Societal Importance of the Research Achievements |
中枢神経系におけるFFAR1の機能に関しては未だ不明な点が多い中、本研究は、コカイン投与による移所運動活性亢進における線条体FFAR1の機能的関与(セロトニン放出促進)を示唆した。本結果は、現在進行している「依存性薬物による行動変化におけるFFAR1の機能的関与」に関する研究を推進するきっかけとなった。
また、FFAR1作動薬が脳内セロトニン遊離に関与することから、FFAR1はうつ・不安様行動にも何らかの機能的役割を持つことが推察され、実際、疼痛などのストレス刺激に伴う情動行動変化に重要な役割を持つことが明らかになりつつある。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] In silico screening identified novel small-molecule antagonists of PAC1 receptor.2018
Author(s)
Takasaki I, Watanabe A, Yokai M, Watanabe Y, Hayakawa, D, Nagashima, R, Fukuchi, M, Okada, T, Toyooka, N, Miyata, A, Gouda H, Kurihara T.
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Journal Title
J. Pharmacol. Exp. Ther.
Volume: -
Issue: 1
Pages: 1-8
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice.2017
Author(s)
Nakamoto K, Aizawa F, Miyagi K, Yamashita T, Mankura M, Koyama Y, Kasuya F, Hirasawa A, Kurihara T, Miyata A, Tokuyama S.
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Journal Title
PLoS One
Volume: 12(7)
Issue: 7
Pages: e0180610-e0180610
DOI
Related Report
Peer Reviewed / Open Access
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