Abstracts

Rationale: Immature rats of an inbred WAG/Rij strain exhibit lower threshold for elicitation of cortical epileptic afterdischarges (CxADs) of the spike-and-wave type than outbred Wistar rats (Mares and Tolmacheva 2004). We decided to compare postictal refractoriness between WAG/Rij and Wistar rats and to analyze the role of GABAB receptors which play an important role in the postictal phenomena in Wistar rats.Methods: Rats 12, 15, 18 and 25 days old with implanted cortical stimulation and registration electrodes were used in these experiments. CxADs were elicited by rhythmic 8-Hz stimulation of sensorimotor cortical region with suprathreshold intensity (3mA in rats 18 and 25 days old, 4-6mA in the two youngest groups. Postictal phenomena – potentiation in 12-day-old rats and refractoriness in 25-day-old ones - were studied by paired cortical stimulations with intervals from 0.5 to 20 min between stimulation series. Pairs of CxADs were repeated in pharmacological experiments where CxADs were affected by a positive allosteric modulator of GABAB receptors CGP7930 (in doses from 5 to 40 mg/kg i.p.) or by an antagonist of these receptors CGP46381 (in doses 3 and 10 mg/kg i.p.).Results: If results were compared with Wistar rats, marked differences were found. A failure of the second stimulation repeated 0.5 min after the end of the first AD (i.e.postictal refractoriness) appeared for the first time at the age of 25 days much later than in Wistar rats. On the contrary, marked potentiation of the second ADs was recorded in 12- and 15-day-old animals not only at the shortest interval but also at 1- and 3-min intervals. Positive allosteric modulator of GABAB receptors CGP7930 suppressed potentiation of the second AD in 12-day-old rats in a dose-dependent manner, leaving intact the refractoriness in 25-day-old animals. The antagonist of GABAB receptors did not significantly change potentiation in 12-day-old rats but markedly attenuated postictal refractoriness in 25-day-old animals.Conclusions: Our results demonstrated delayed development of postictal refractoriness in WAG/Rij rats in comparison with Wistar animals. An important role of GABAB system in postictal phenomena was confirmed also in WAG/Rij rats. This study was supported by a grant No.15-16605S of Grant Agency of the Czech Republic and by projects No.LC-554 of the Ministry of Education and No.RVO 67985823 of the Czech Academy of Sciences.