{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T23:42:38Z","timestamp":1773704558482,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>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 (\u2212\/\u2212) 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 \u2212\/\u2212 mice. Although acute administration of cocaine enhanced the locomotor activity in both +\/+ and \u2212\/\u2212 mice, the magnitude of the enhancement was significantly reduced in \u2212\/\u2212 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.<\/jats:p>","DOI":"10.3389\/fphar.2021.699026","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T06:34:42Z","timestamp":1629441282000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["FFAR1\/GPR40 Contributes to the Regulation of Striatal Monoamine Releases and Facilitation of Cocaine-Induced Locomotor Activity in Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Yuko","family":"Sadamura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanta","family":"Thapa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Mizunuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Kambe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Hirasawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Nakamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shogo","family":"Tokuyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Yoshimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunori","family":"Arita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuro","family":"Miyata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuki","family":"Oyoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kurihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8156","DOI":"10.1523\/JNEUROSCI.3905-08.2009","article-title":"Impact of Serotonin 2C Receptor Null Mutation on Physiology and Behavior Associated with Nigrostriatal Dopamine Pathway Function","volume":"29","author":"Abdallah","year":"2009","journal-title":"J. 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