Failure of the antiepileptic drug valproic acid to modify synaptic and non-synaptic responses of CA1 hippocampal pyramidal cells maintained 'in vitro'.

The mechanisms of action of the antiepileptic drug valproic acid (VPA) were analyzed in 24 CA1 pyramidal neurons of the 'in vitro' hippocampal slice by using standard intracellular recording techniques. VPA (0.5-2 mM) failed to induce any significant change in the amplitude of the orthodromic EPSPs and the amplitude and duration of the IPSPs evoked by orthodromic or antidromic stimuli. The repetitive firing induced by depolarizing current pulses and the subsequent long lasting afterhyperpolarization were also not affected by VPA. We conclude that VPA, at doses within the therapeutic range, does not potentiate GABA-mediated inhibition in this preparation and probably acts on mechanisms which are not operating or fully expressed in normal (i.e., non-epileptic) situations.