VALPROIC ACID SUPPRESSES THE SYNAPTIC RESPONSE MEDIATED BY THE NMDA RECEPTORS IN RAT AMYGDALAR SLICES

The mechanism of action of the anticonvulsant drug valproic acid (VPA) was studied in rat amygdaloid slices using intracellular recording te chniques. In the presence of bicuculline (20 muM), stimulation of the endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP ) followed by a paroxysmal depolarizing shift (PDS). Superfusion of VP A (2 mM) reversibly suppressed the PDS. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptors (EPSP(NMDA)) was isolated ph armacologically by application of a solution containing nonNMDA recept or antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and gamma-am inobutyric acid receptor antagonist bicuculline (20 muM). VPA (0.2-10 mM) reversibly reduced the amplitude of the EPSP(NMDA) in a dose-depen dent manner. Higher concentration of VPA (10 mM), in addition, suppres sed the normal synaptic transmission. These results suggest that VPA's anticonvulsant effect is due, at least in part, to its blocking actio n on the EPSP(NMDA).