Abstracts

Rationale: Postictal refractoriness may be taken as an expression of active mechanisms arresting seizures. This phenomenon is present not only in adult rats but also in 25-day-old animals. Therefore we started to analyze a role of neurotransmitter systems in postictal refractoriness after cortical seizures. Methods: Cortical epileptic afterdischarges (ADs) elicited in freely moving 25-day-old rats were used as a model seizures. Stimulation of sensorimotor cortex with suprathreshold intensity elicited ADs; one minute after the end of AD the same stimulation was applied again. Then the drugs affecting neurotransmitter systems - inhibitory GABAergic (GABAA receptor antagonists bicuculline, picrotoxin, pentetrazol, benzodiazepine receptor inverse agonist Ro 19-4603, GABAB receptor antagonist CGP35348), adenosinergic (caffeine), opioid (mju receptor antagonist naloxone); excitatory glutamatergic (N-methyl-D-aspartate and kainate as prototypic agonists) were administered in subconvulsant doses and after ten minutes the paired stimulation was repeated. Results: Under control conditions second stimulation 1 min after the first AD did not elicit a new AD. Antagonists of GABAA, GAGAB and adenosine receptors led to prolongation of the first AD. Drugs suppressing inhibition mediated by GABAA receptors did not affect postictal refractoriness whereas an antagonist of GABAB receptors CGP35348 and nonspecific adenosine receptor antagonist caffeine resulted in a partial block of refractoriness - second stimulation elicited AD but the duration was shorter than that of the first one. Partial block was also achieved with naloxone. On the other hand, augmentation of excitation did not lead to a block of poastictal refractoriness. Conclusions: GABAB, adenosine and mju opioid receptors participate in postictal refractoriness after cortical ADs whereas the role of GABAA and ionotropic glutamate receptors is negligible. Refractoriness after cortical epileptic afterdischarges thus differ from that after hippocampal afterdischarges which may be abolished by a block of mju opioid receptors with naloxone. This study was supported by a collaborative US-Czech grant No.LH11015 and by research projects AV0Z50110509 and RVO:67985823.