FFAR1/GPR40はマウス線条体におけるモノアミン放出の調節およびコカイン誘発移所運動活性亢進に寄与している

• Material Type: 博士論文
• Title: FFAR1/GPR40はマウス線条体におけるモノアミン放出の調節およびコカイン誘発移所運動活性亢進に寄与している
• Author/Editor: 貞村, 祐子
• Author Heading: 貞村, 祐子 サダムラ, ユウコ
• Publication, Distribution, etc.: Frontiers
• Alternative Title: FFAR1/GPR40 Contributes to the Regulation of Striatal Monoamine Releases and Facilitation of Cocaine-Induced Locomotor Activity in Mice
• Degree grantor/type: 鹿児島大学
• Date Granted: 2022-01-18
• Dissertation Number: 甲総研第627号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Text Language Code: eng
• Subject Heading: FFAR1; GPR40; serotonin; 5-HT; cocaine; locomotor activity; striatum
• Target Audience: 一般
• Note (General): 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨; The free fatty acid receptor 1 (FFAR1) is suggested to function as a G protein-coupled receptor (GPR40) for medium-to-long-chain free fatty acids. Previous studies on the expression of FFAR1 revealed that the nigrostriatal region is one of the areas which express abundant FFAR1 mRNA/protein in the central nervous system (CNS). However, the role of FFAR1 in the CNS has been still largely unclarified. Here, we examined a possible functional role of FFAR1 in the control of extracellular concentrations of striatal monoamines and cocaine-induced locomotor activity. Microdialysis analysis revealed that the basal level of extracellular dopamine (DA) was significantly elevated, while the basal serotonin (5-HT) level tended to be reduced in the striatum of FFAR1 knockout (−/−) mice. Interestingly, local application of a FFAR1 agonist, GW9508, markedly augmented the striatal 5-HT release in FFAR1 wild-type (+/+) mice, whereas topical application of a FFAR1 antagonist, GW1100, significantly reduced the 5-HT release. However, the enhanced 5-HT release was completely lost in −/− mice. Although acute administration of cocaine enhanced the locomotor activity in both +/+ and −/− mice, the magnitude of the enhancement was significantly reduced in −/− mice. In addition, intraperitoneal injection of GW1100 significantly decreased the cocaine-induced locomotor enhancement. These results suggest that FFAR1 has a facilitatory role in striatal 5-HT release, and the evoked 5-HT release might contribute to enhance cocaine-induced locomotor activity. Yuko Sadamura, Shanta Thapa, Ryota Mizunuma, Yuki Kambe, Akira Hirasawa, Kazuo Nakamoto, Shogo Tokuyama, Koji Yoshimoto, Kazunori Arita, Atsuro Miyata, Tatsuki Oyoshi, Takashi Kurihara FFAR1/GPR40 Contributes to the Regulation of Striatal Monoamine Releases and Facilitation of Cocaine-Induced Locomotor Activity in Mice Frontiers in Pharmacology 12, 699026, 2021 https://doi.org/10.3389/fphar.2021.699026
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ

Table of Contents

Result_Sadamura_Yuko_isk_627 other

Comments_Sadamura_Yuko_isk_627 other

Diss_貞村_祐子_ISK627_2021 fulltext

Abstract_貞村_祐子_4512810013_2021 abstract