{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T20:59:35Z","timestamp":1774817975438,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"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:sec><jats:title>Aim<\/jats:title><jats:p>Previous studies have demonstrated that Ras-related GTP-binding protein Rab10 (Rab10) plays a role in psychostimulant-induced behavioral effects. In this study, we showed that Rab10 in the nucleus accumbens (NAc) of male animals affects the development of cocaine-induced behavioral effects, which are associated with the plasma membrane expression of the GABA<jats:sub>B<\/jats:sub> heteroreceptor (GABA<jats:sub>B<\/jats:sub>R).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed flow cytometry, immunoendocytosis, pHluorin activity analysis, electrophysiology analysis, and open-field testing to explore the role of Rab10 in modulating the membrane expression and function of GABA<jats:sub>B<\/jats:sub>R and its regulatory effect on cocaine-induced behavioral effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transcriptomics analysis showed that <jats:italic>Rab10<\/jats:italic> was elevated following acute cocaine treatment. Membrane levels of Rab10 increased within day 1 of the cocaine treatment, subsequently decreasing at later time points. <jats:italic>Rab10<\/jats:italic> deficiency in NAc regions significantly increased cocaine-inhibited membrane GABA<jats:sub>B<\/jats:sub>R levels and inhibited cocaine-induced hyperlocomotion and behavioral sensitization. In addition, <jats:italic>GAD<\/jats:italic><jats:sub><jats:italic>67<\/jats:italic><\/jats:sub><jats:sup><jats:italic>+<\/jats:italic><\/jats:sup>-expressing neurons from NAc regions treated with cocaine revealed a significant decrease in Rab10 membrane expression. Furthermore, NAc neuron-specific <jats:italic>Rab10<\/jats:italic> knockout resulted in a significant increase in the cocaine-inhibited membrane expression of GABA<jats:sub>B<\/jats:sub>R, along with increased miniature inhibitory postsynaptic current (mIPSC) amplitude and attenuation of baclofen-amplified Ca<jats:sup>2+<\/jats:sup> influx.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results uncover a new mechanism in which Rab10-GABA<jats:sub>B<\/jats:sub>R signaling may serve as a potential pathway for regulating cocaine-induced behavioral effects.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1496657","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T04:33:52Z","timestamp":1732682032000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of Rab10 in cocaine-induced behavioral effects is associated with GABAB receptor membrane expression in the nucleus accumbens"],"prefix":"10.3389","volume":"15","author":[{"given":"Zhuoxuan","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyun","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caidi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingfen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghua","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s00213-004-1968-6","article-title":"Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates","volume":"177","author":"Brebner","year":"2005","journal-title":"Psychopharmacol. 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