FELBAMATE DECREASES SYNAPTIC TRANSMISSION IN THE CA1 REGION OF RAT HIPPOCAMPAL SLICES

The antiepileptic drug felbamate (FBM) is known to block N-methyl-o-as partate receptor-mediated responses and to decrease voltage-sensitive Na+ and Ca++ channels. The present work was aimed at investigating the actions of FBM on synaptic potentials in the hippocampus, a region fr equently involved in epileptic discharges. In rat hippocampal slices, application of FBM (100-1300 mu M, 10 min) elicited a concentration-de pendent, fully reversible decrease in amplitude of electrically evoked population spikes recorded extracellularly from the CA1 pyramidal cel l layer. In intracellular recordings, FBM (50-300 mu M) decreased the amplitude of excitatory postsynaptic potentials and reduced the probab ility of firing action potentials upon synaptic activation. Action pot ential frequency adaptation (accommodation), which typically limits re petitive firing in CA1 pyramidal cells, was increased. By using a pair ed-pulse protocol, FBM (300 mu M) depressed the amplitude of paired ex citatory postsynaptic potentials, without affecting the facilitation o f the second response. In nominally Mg++-free solution, FBM (100 mu M) blocked N-methyl-D-aspartate receptor-mediated synaptic excitatory po stsynaptic potentials isolated by the presence of 10 mu M 6-nitro-7-su lfamoylbenzo(f)quinoxaline hydrochloride, a selective lpha-amino-3-hyd roxy-5-methylisoxazole-4-propionic acid receptor antagonist, and 10 mu M bicuculline or 25 mu M picrotoxin. This effect was not reversed by the addition of 300 mu M Gly. All these effects contribute to decrease excitatory synaptic transmission and are likely to limit neuron recru itment and propagation of epileptic discharges.