Augmentation of Tonic GABAA Inhibition in Absence Epilepsy: Therapeutic Value of Inverse Agonists at Extrasynaptic GABAA Receptors
Loss of functional GAT-1 in TC neurons leads to SWDs. (a) In adult (P68-74) GAT-1−/− mice, tonic GABAA currents in VB TC neurons are significantly larger than in WT littermates. (b) Simultaneous bilateral EEG traces reveal that adult GAT-1−/− mice also display SWDs (WT animals did not display SWDs—data not shown). The spectrogram at the bottom corresponds to the EEG signal from the right (R) hemisphere. (c) Treatment of GAT-1−/− mice with the anti-absence drug ethosuximide (200 mg per kg body weight i.p.) significantly reduces the total time spent in seizures. (d) Bilateral EEG traces from a normal Wistar rat following intrathalamic administration by reverse microdialysis of 200 μM of the selective GAT-1 blocker NO711 (spectrogram of the L trace is illustrated below). (e) Time course of the induction of SWDs by intrathalamic administration of NO711. (a–e) reproduced from .
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