Abstracts

Rationale: Postictal refractoriness, i.e. an inability to elicit new seizures immediately after the end of the first one, may be taken as an expression of overlasting inhibitory mechanisms arresting the first seizure. These mechanisms must not be the same in different brain structures; on the background of our recent finding that antagonists of GABA-B receptors substantially prolong duration of cortical afterdischarges in immature rats (Mares 2010) we focused attention on this system.Methods: Experiments were performed on rats 12 or 25 days old with implanted epidural stimulation and recording electrodes. The two age groups were chosen on basis of our data, that postictal refractoriness is absent in 12-day-old rats (the control stimulations demonstrated the second AD longer than the first one) whereas 25-day-old animals exhibit fully developed postictal refractoriness (only a part of rats exhibited a short AD with average duration less than 10% of the first one). Suprathreshold low-frequency cortical stimulation (15-s series of 1-ms biphasic pulses at 8-Hz frequency) was repeated one min after the end of an epileptic afterdischarge, then GABA-B receptor antagonist CGP46381 (in a dose of 3 or 10 mg/kg) or positive allosteric modulator CGP7930 (20 or 40 mg/kg) was administered intraperitoneally and the paired stimulations were repeated 10 min after the injection. Incidence and duration of AD were evaluated.Results: Comparison of the two age groups confirmed an absence of postictal refractoriness in 12-day-old rats and its presence in 25-day-old animals. GABA-B receptor antagonist did not change the situation in 12-day-old rats whereas it partially suppressed refractoriness in the older group. The second stimulation elicited an AD in 6 out of 11 and 5 out of 9 rats with the 3- and 10-mg/kg dose of CGP 46381, respectively. As concerns the duration of ADs, the lower dose was more efficient than the higher one, the average duration of the second AD after the 3-mg/kg dose was nearly 50% of the first one. Positive allosteric modulator CGP7930 did not affect the situation in either age group.Conclusions: Already existing refractoriness after cortical epileptic afterdischarges can be partly suppressed by a GABA-B receptor antagonist CGP 46381. On the other hand, positive allosteric modulator CGP 7930 was not able to establish postictal refractoriness in immature rats where this phenomenon is not yet present. This study was supported by grant No.P304/10/1274 of the Grant Agency of the Czech Republic and by a collaborative US-Czech project No.LH11015