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Neurosci."],"accepted":{"date-parts":[[2026,3,1]]},"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:p>\n                    Many antiepileptic drugs act by modulation of ionotropic GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors or effects on extracellular GABA concentrations. Metabotropic GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptors also affect neuronal excitability but are not recognized as a target of antiepileptic drugs. We investigated effects of GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptors and antiepileptic drug vigabatrin on epileptiform discharges induced by 4-aminopyridine (4AP) in hippocampal brain slices from male mice. The GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptor agonist baclofen caused dose-dependent reduction in frequency of 4AP-induced epileptiform discharges but did not affect amplitude or duration of discharges. The inhibitory effects of baclofen were blocked by GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptor antagonist CGP55845 (CGP) and the K\n                    <jats:sup>+<\/jats:sup>\n                    channel blocker Ba\n                    <jats:sup>2+<\/jats:sup>\n                    , indicating that baclofen was acting on GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptors and activating GIRK channels. Baclofen effects were independent of GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors. Vigabatrin inhibits GABA transaminase, thereby increasing GABA concentrations. Pretreatment of brain slices with vigabatrin suppressed 4AP-induced discharges, significantly prolonging the latency to onset of spontaneous activity and reducing frequency of discharges. Similar to baclofen, vigabatrin effects on latency and frequency were reversed by GABA\n                    <jats:sub>B<\/jats:sub>\n                    antagonist CGP and the GIRK channel blocker Ba\n                    <jats:sup>2+<\/jats:sup>\n                    . Vigabatrin had no effect on 4AP-induced activity in GABA transporter type 1 knock-out mice (GAT1KO), suggesting that vigabatrin effects are dependent on GAT1 function. Our results indicate for the first time that a clinically used antiepileptic drug (vigabatrin) suppresses in vitro epileptiform activity via activation of GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptors and GIRK channels. Data are consistent with a model that depicts altered thermodynamic equilibrium of GAT1 after GABA transaminase inhibition that leads to elevated extracellular GABA concentration and activation of GABA\n                    <jats:sub>B<\/jats:sub>\n                    receptors.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.1075-25.2026","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:55:18Z","timestamp":1773338118000},"page":"e1075252026","update-policy":"https:\/\/doi.org\/10.1523\/jneurosci.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Suppression of In Vitro Epileptiform Activity by GABA Transaminase Inhibition Is Dependent on GABA\n                    <sub>B<\/sub>\n                    Receptors and GABA Transporter Type 1 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