Medical Neurobiology Commons^™

Topiramate Reduces Excitability In The Basolateral Amygdala By Selectively Inhibiting Gluk1 (Glur5) Kainate Receptors On Interneurons And Positively Modulating Gaba-A Receptors On Principal Neurons, Maria Braga, Vassiliki Aroniadou-Anderjaska, He Li, Michael Rogawski

Michael A. Rogawski

Topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] is a structurally novel antiepileptic drug that has broad efficacy in epilepsy, but the mechanisms underlying its therapeutic activity are not fully understood. We have found that topiramate selectively inhibits GluK1 (GluR5) kainate receptor-mediated excitatory postsynaptic responses in rat basolateral amygdala (BLA) principal neurons and protects against seizures induced by the GluK1 kainate receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA). Here, we demonstrate that topiramate also modulates inhibitory function in the BLA. Using whole-cell recordings in rat amygdala slices, we found that 0.3 to 10 microM topiramate 1) inhibited ATPA-evoked postsynaptic currents recorded from BLA interneurons; 2) suppressed ATPA-induced …