Zonisamide at clinically relevant concentrations inhibits field EPSP but not presynaptic fiber volley in rat frontal cortex

We investigated the effect of Zonisamide (ZNS), a newer anti-epileptic drug, on field potentials and neuropropagation in rat frontal cortex, with the aid of the 64-channel multi-electrode dish (MED64) system. The amplitude and propagation of field potentials were expressed dimensionally in the MED64 system. ZNS (3-100 μM) inhibited the amplitude and propagation of field excitatory postsynaptic potentials (fEPSP) in a concentration dependent manner. In contrast, ZNS could not suppress the amplitude and propagation of the presynaptic fiber volley (PrV) at clinically relevant concentrations (10-30 μM). Stimulating dependency with reduction fEPSP was seen in the presence of ZNS at clinically relevant concentrations, but not with PrV. The reduction of fEPSP amplitude was not accompanied by a change in paired-pulse facilitation. These data suggest that at clinically relevant concentrations of ZNS, the suppression of neuronal propagation is at least partially due to the postsynaptic mechanism, probably through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.