Antiepileptic effect of carbenoxolone on seizures induced by 4-aminopyridine: a study in the rat hippocampus and entorhinal cortex.

We have examined the effects of the gap junction blocker carbenoxolone (CBX) on the generation and propagation of epileptiform activity induced by 4-aminopyridine (4-AP) in the rat entorhinal cortex and hippocampus. We analyzed the epileptiform pattern generated on awaked rats by administering 10 nmol of 4-AP and we studied the effect of administering CBX (50 nmol) 30 min later by injection into the entorhinal cortex. The injection of 4-AP produced an epileptiform pattern in EEG recordings characterized by an initial hypersynchronic activity followed by trains of high-amplitude epileptiform discharges. This pattern was associated with convulsive behavior rated as 0, 1 and 3 in the Racine Scale. In contrast, no changes in electrical activity or behavior were observed in animals that received NaCl or CBX alone. The application of CBX to rats that had received 4-AP decreased the amplitude and frequency of the epileptiform discharges, as well as the number and duration of the epileptiform trains in the entorhinal cortex and hippocampus. Indeed, discharge trains were completely blocked by CBX after 22+/-4.4 min, and likewise CBX reverted the convulsive behavior of these animals. We conclude that Gap junctions participate in the generation and propagation of epileptiform activity induced by 4-AP in these regions, as well as blocking motor alterations.