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Abuse of psychoactive drugs, such as caffeine (CAFF), generates changes in cognitive functions. The main pharmacological targets of CAFF are mainly the A\n                    <jats:sub>1<\/jats:sub>\n                    R and A\n                    <jats:sub>2A<\/jats:sub>\n                    R adenosine receptors, which can regulate GABA homeostasis. We therefore evaluated the influence of CAFF intake upon GABA uptake and release in the frontal cortex (FC) of adolescent Swiss mice and addressed the underlying mechanism. Mice were treated for 5\u2009days with a subcutaneous injection of CAFF (10, 20, and 40\u2009mg\/kg) every 24\u2009h, and the FC dissected out at 1\u2009h after the last injection for measurement of [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010GABA uptake and release, cAMP accumulation, and density levels of GAT\u20101, A\n                    <jats:sub>1<\/jats:sub>\n                    R, A\n                    <jats:sub>2A<\/jats:sub>\n                    R, PKA, and PKC. Calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) imaging was performed on primary neuronal cultures treated with CAFF (200\u2009\u03bcM). CAFF increased [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010GABA uptake at all doses studied, an effect reversed by incubation with the selective GAT\u20101 uptake inhibitor, NO\u2010711 (10\u2009\u03bcM). At 20 and 40\u2009mg\/kg, CAFF also increased [\n                    <jats:sup>3<\/jats:sup>\n                    H]\u2010GABA release. CAFF also increased A\n                    <jats:sub>1<\/jats:sub>\n                    R, but not A\n                    <jats:sub>2A<\/jats:sub>\n                    R levels. The influence of CAFF involves pPKC activity since CAFF enhanced the pPKC\/PKC ratio, while the PKC\u2010inhibitor G\u00f6 6983 (100\u2009nM) reversed the facilitatory action of CAFF upon GABA transport and prevented the CAFF\u2010induced increase in the frequency of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transients in neuronal cell cultures. We conclude that CAFF alters GABAergic homeostasis in the FC, increasing GABA transport through PKC\u2010activity modulation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70520-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70520","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:31:32Z","timestamp":1783931492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Caffeine Regulates\n                    <scp>GABA<\/scp>\n                    Transport Homeostasis in the Adolescent Mouse Frontal Cortex via Adenosine\n                    <scp>A1<\/scp>\n                    Receptor and\n                    <scp>PKC<\/scp>\n                    \u2010Dependent Pathways"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7177-7226","authenticated-orcid":false,"given":"Robertta Silva","family":"Martins","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Neurofarmacologia, Instituto Biom\u00e9dico Universidade Federal Fluminense  Niter\u00f3i Brazil"},{"name":"Laborat\u00f3rio de Neurobiologia Celular e Molecular, Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro  Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5213-0363","authenticated-orcid":false,"given":"Vladimir Pedro 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