Felbamate decreases synaptic transmission in the CA1 region of rat hippocampal slices.
The antiepileptic drug felbamate (FBM) is known to block N-methyl-D-aspartate receptor-mediated responses and to decrease voltage-sensitive Na+ and Ca+2 channels. The present work was aimed at investigating the actions of FBM on synaptic potentials in the hippocampus, a region frequently involved in epileptic discharges. In rat hippocampal slices, application of FBM (100-1300 microM, 10 min) elicited a concentration-dependent, fully reversible decrease in amplitude of electrically evoked population spikes recorded extracellularly from the CA1 pyramidal cell layer. In intracellular recordings, FBM (50-300 microM) decreased the amplitude of excitatory postsynaptic potentials and reduced the probability of firing action potentials upon synaptic activation. Action potential frequency adaptation (accommodation), which typically limits repetitive firing in CA1 pyramidal cells, was increased. By using a paired-pulse protocol, FBM (300 microM) depressed the amplitude of paired excitatory postsynaptic potentials, without affecting the facilitation of the second response. In nominally Mg(+2)-free solution, FBM (100 microM) blocked N-methyl-D-aspartate receptor-mediated synaptic excitatory postsynaptic potentials isolated by the presence of 10 microM 6-nitro-7-sulfamoylbenzo(f)quinoxaline hydrochloride, a selective alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, and 10 microM bicuculline or 25 microM picrotoxin. This effect was not reversed by the addition of 300 microM Gly. All these effects contribute to decrease excitatory synaptic transmission and are likely to limit neuron recruitment and propagation of epileptic discharges.
Pugliese
A M
AM
Dipartimento di Farmacologia Preclinica e Clinica Mario Aiazzi-Mancini, Università di Firenze, Italy.
Passani
M B
MB
Pepeu
G
G
Corradetti
R
R
D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D000078328:Felbamate; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D048448:Phenylcarbamates; D011409:Propylene Glycols; D016194:Receptors, N-Methyl-D-Aspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid; D000078328:Felbamate