Biphasic action of vigabatrin on cortical epileptic after-discharges in rats

The time course of the anticonvulsant effect of vigabatrin against cortically induced epileptic after-discharges (ADs) was studied in freely moving rats with implanted electrodes. Adult rats (n=30) were exposed to five stimulation sessions each consisting of six stimulation series at 20-min intervals. The first session was a control one, then two groups of animals (n=10 each) were given vigabatrin (600 or 1,200 mg/kg i.p.), the control animals received physiological saline. Stimulation sessions were repeated 1, 24, 48, and 96 hours after the injection. Control animals exhibited an increased transition from the spike-and-wave type of AD to the second, "limbic" type and an increased intensity of movements accompanying stimulation. ADs in the second and subsequent sessions were, however, shorter than in the first session. Vigabatrin facilitated the transition to the second type of AD 1 h after administration but suppressed this transition as well as decreased the number of stimulations eliciting ADs 48 h later. AD duration and the severity of clonic seizures accompanying spike-and-wave ADs were influenced similarly. The effects of the lower dose of vigabatrin were more marked than those of the higher dose. The biphasic action of vigabatrin in our model might be due either to uneven changes of GABA concentration in different brain structures or to an additional mechanism of action. Our results in a cortical model of seizure demonstrate that the sequence of pro- and anticonvulsant actions of vigabatrin is not restricted to seizures of limbic origin and might represent a general phenomenon.