Influence of Carbenoxolone on the Anticonvulsant Efficacy of Phenytoin in Pentylenetetrazole Kindled Rats

Abstract

Abnormal synchronized neuronal discharges mediated by gap junctions have an important role in epileptic seizures. The analysis of anticonvulsant drugs acting on gap junctions is still a priority in epilepsy research. Therefore, the present study was designed to investigate the effect of carbenoxolone, a gap junction blocker, on the anticonvulsant efficacy of phenytoin in pentylenetetrazole kindled rats. Male Wistar albino rats, 14 weeks of age, were used. In the first step of the study, animals were given PTZ 35 mg/kg intraperitoneally (i.p.) three times a week until kindling was produced. Then, indwelling screw electrodes - allowing EEG monitoring of conscious rats - were implanted into the crania of the kindled rats. In this way, we were able to record EEG activity and evaluate seizure stage at the same time. In the second step of the study, the interaction between carbenoxolone (40 mg/kg i.p.) and phenytoin (60 mg/kg, i.p.) was investigated. The data analysis was performed using a one-way ANOVA with LSD post-hoc test. Total spike number and the generalized seizure duration were reduced in the carbenoxolone treated group compared to the PTZ group. Phenytoin decreased generalized seizure duration, total spike number and seizure severity score. Carbenoxolone and phenytoin have anti-seizure effects in PTZ kindled rats. There was no significant difference between the carbenoxolone + phenytoin combination and phenytoin in terms of generalized seizure duration, total spike number and seizure stage. The results indicate that carbenoxolone combined with phenytoin is not more effective than the use of these drugs alone. © 2012 by Polish Neuroscience Society - PTBUN, Nencki Institute of Experimental Biology.