Pentylenetetrazol elicits epileptiform activity in the dentate gyrus of the urethane anesthetized rat by activation of the entorhinal cortex.

Pentylenetetrazol is a chemical convulsant, often used to generate experimental seizures, that is thought to act as a GABA antagonist. In the urethane anesthetized rat, pentylenetetrazol produces a characteristic epileptiform discharge in the dentate gyrus. The hypothesis that this discharge is generated by activity in the entorhinal cortex was examined in this study. Recording electrodes were placed in the dentate gyrus bilaterally and neuronal activity was recorded after administration of pentylenetetrazol. A laminar analysis of the convulsant-induced activity was compared to responses evoked by angular bundle stimulation (n = 6). Both convulsant-induced and evoked activity were negative-going in the molecular layer of the dentate gyrus. In other animals tetrodotoxin (TTX) was injected into the right entorhinal cortex before the onset of epileptiform activity (n = 5). The TTX prevented epileptiform activity in the right dentate gyrus. Injection of TTX after the onset of epileptiform activity caused the epileptiform activity to cease on the side of injection (n = 5). These experiments support the hypothesis that pentylenetetrazol specifically activates the entorhinal cortex to produce the epileptiform activity recorded in the dentate gyrus. This selective activation suggests that the mechanism of action of pentylenetetrazol, as a convulsant, is not simply as an antagonist of GABA receptors.