Ethosuximide specifically antagonizes the effect of pentylenetetrazol in the rat entorhinal cortex

This study tested two related hypotheses. The first is that the entorhinal cortex has an important role in synchronization and spread of epileptiform activity into the dentate gyrus. The second is that ethosuximide acts by antagonizing the action of pentylenetetrazol (PTZ) in the entorhinal cortex. Experiments were carried out in urethane anesthetized rats. Recording electrodes were placed in the dentate gyrus and stimulating electrodes were placed in the angular bundle. Administration of PTZ reduced the time to onset of maximal dentate activation, which is a marker for synchronized reverberatory seizure activity in the hippocampal-parahippocampal circuits. Since PTZ facilitates the spread of epileptiform activity in, or through, the entorhinal cortex, these results support the hypothesis that the entorhinal cortex can influence the spread of seizure activity from the entorhinal cortex into the hippocampus. Ethosuximide specifically, and dose-dependently, reduced the polysynaptic response in the dentate gyrus that is initiated by PTZ, while having no effect on the response in the dentate gyrus to ipsilateral angular bundle stimulation. These results support the hypotheses that ethosuximide can antagonize this effect of PTZ.