Levetiracetam effect and electrophysiological mechanism of action in rats with cobalt-induced chronic epilepsy

Abstract

Levetiracetam was initially developed as a nootropic drug, although since 2002 it has been used as anticonvulsant for the treatment of partial and generalized epilepsy syndromes. The purpose of the research was to investigate anti-paroxysmal activity of levetiracetam (LEV) on the model of cobalt-induced chronic epilepsy caused by the application of cobalt to the sensorimotor area of the rat cortex to evaluate LEV impact on the different stages of epileptogenesis. LEV effects were studied at the initial stage of the epileptogenesis (2nd day after the cobalt application) and at the stage of generalized paroxysmal activity (6th day after the cobalt application). The research showed that levetiracetam administration (dosages 50 mg/kg and 200 mg/kg) at the early stage of the epileptogenesis had no statistically significant effect on the development of paroxysmal activity in both primary and secondary epileptic areas: in the ipsi- and contralateral cortex, hypothalamus and hippocampus. LEV administration on 6th day (dosage 50 mg/kg) did not have statistical effect on the epileptogenesis, while at a dosage of 200 mg/kg on 6th day LEV significantly suppressed paroxysmal activity in the studied structures of rats with cobalt epilepsy. The strongest anti-paroxysmal effect was detected in hippocampus and was expressed as the normalization of bioelectrical activity and the appearance of a regular theta rhythm. Thus, LEV effects are mostly directed to the hippocampal area of epileptiform activity and, to a lesser extent, to the cortical area.