Sodium valproate decreases synaptic potentiation and epileptiform activity in hippocampus.

The actions of sodium valproate (NaVP) were studied in the in vitro hippocampus using extracellular, intracellular and voltage-clamp recording techniques. In the CA1 region, concentrations of 30-200 microM NaVP reduced the amplitude but not the time course of post-tetanic potentiation (PTP) of dendritic field excitatory postsynaptic potentials (EPSPs). Epileptiform discharges were studied intracellularly in CA3 cells after pharmacological blockade of synaptic inhibition and repeated tetanic stimulation. NaVP (100 microM) blocked evoked paroxysmal depolarizing shift (PDS) discharges through a mechanism of increasing the threshold for burst-firing. When the PDS current was studied under voltage-clamp, application of NaVP (100 microM) resulted in a graded reduction of the PDS waveform. All of the actions of NaVP may result from inhibition of excitatory synaptic transmission following repetitive cell firing. A hypothesis is proposed that NaVP may act to decrease excitatory synaptic potentiation necessary for network synchronization.