Abstracts

Rationale: Postictal depression including postictal refractoriness was repeatedly described and analyzed. In contrast, postictal potentiation present in immature brain is neglected. We described the action of excitatory amino acid antagonists on this phenomenon and decided to study effects of augmentation of inhibitory systems. Methods: Experiments were performed in 12-day-old rat pups with implanted cortical stimulation and registration electrodes. Epileptic afterdischarges (CxAD) were elicited by 15-s series of 8-Hz pulses with suprathreshold intensity. One min after the end of the first, conditioning CxAD the stimulation was repeated and immediately after the end of the second, testing CxAD the drugs were injected intraperitoneally and 10 min later the paired stimulation was repeated. Duration of CxADs was measured and testing CxADs were compared to the appropriate conditioning CxADs.Drugs acting on GABAA receptors muscimol (0.2 and 0.5 mg/kg) and midazolam (0.1 and 0.2 mg/kg) as well as allosteric positive modulator of GABAB receptors CGP7930 (20 and 40 mg/kg) and adenosine A1 agonist CCPA (0.5 and 1 mg/kg) were used . Results: GABAA agonist muscimol did not affect the duration of CxADs whereas benzodiazepine midazolam markedly shortened duration of both conditioning and testing CxADs. Similar but moderate effect was found after CGP7930 administration but this result is not clear because of effect of solvent (DMSO). Adenosine A1 agonist resulted in marked shortening of conditioning ad well as testing CxADs. Conclusions: In contrast to antagonists of NMDA receptors agonists of three inhibitory systems failed to selectively affect postictal potentiation. Anticonvulsant action of agonists of GABAA and adenosine A1 receptors is expressed as shortening of both conditioning and testing CxADs. Funding: This study was supported by a grant of the Ministry of Education of the Czech Republic No.LH15032 and grants of the Czech Science Foundation No.15-16605S and P304/12/G069.