Verification of the importance of central FFAR1 system in nociceptive and emotional behaviors in mice

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10792
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kagoshima University
• Principal Investigator: OYOSHI Tatsuki 鹿児島大学, 医歯学域附属病院, 講師 (80315407)
• 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)
• Project Period (FY): 2016-04-01 – 2019-03-31
• 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

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.

Free Research Field

脳神経外科学分野

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。