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 techniques. In the presence of bicuculline (20 microM), stimulation of the endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP) followed by a paroxysmal depolarizing shift (PDS). Superfusion of VPA (2 mM) reversibly suppressed the PDS. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptors (EPSPNMDA) was isolated pharmacologically by application of a solution containing nonNMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and gamma-aminobutyric acid receptor antagonist bicuculline (20 microM). VPA (0.2-10 mM) reversibly reduced the amplitude of the EPSPNMDA in a dose-dependent manner. Higher concentration of VPA (10 mM), in addition, suppressed the normal synaptic transmission. These results suggest that VPA's anticonvulsant effect is due, at least in part, to its blocking action on the EPSPNMDA.