Complex effects of eslicarbazepine on inhibitory micro networks in chronic experimental epilepsy

Objective Many antiseizure drugs (ASDs) act on voltage-dependent sodium channels, and the molecular basis of these effects is well established. In contrast, how ASDs level neuronal networks much less understood. Methods present study, we determined eslicarbazepine (S-Lic) different types inhibitory neurons, as motifs. Experiments were performed in hippocampal slices from both sham-control chronically epileptic pilocarpine-treated rats. Results We found that S-Lic causes an unexpected reduction feed-forward inhibition CA1 region at high concentrations (300 µM), but not lower (100 µM). Concurrently, 300 100 μM significantly reduced maximal firing rates putative interneurons located stratum radiatum animals. feedback was inhibited by S-Lic. Instead, application S-Lic, contrast to previous data for other like carbamazepine (CBZ), resulted a lasting potentiation post-synaptic currents (IPSCs) only animals, which persisted after washout hypothesized this plasticity might rely anti-Hebbian excitatory inputs onto oriens-lacunosum moleculare (OLM) interneurons, dependent Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Indeed, show blocking AMPA receptors completely prevents upmodulation inhibition. Significance These results suggest affects circuits ways. addition, ASD actions may be sufficiently explained acute their target rather, it necessary take into account.