Abstracts

Antagonists of ionotropic excitatory amino acid receptors were shown to exhibit anticonvulsant action in adult as well as immature laboratory rats. The aim of our study was to compare action of antagonists of two types of ionotropin glutamate receptors on phenomena elicited by stimulation of sensorimotor cortex. Stimulation electrodes were implanted to Wistar rat pups 12, 18 and 25 days old over the right sensorimotor cortical area. Three recording electrodes were on the left hemisphere, the fourth one over the right occipital area. Rhythmic stimulation (series of biphasic pulses lasting 1 ms; frequency = 8 Hz; duration = 15 s) was repeated with an increasing current intensity in steps from 0.2 to 14 mA. EEG activity and motor phenomena were recorded. An action of a noncompetitive NMDA antagonist dizocilpine (MK-801, dissolved in saline) and a competitive AMPA antagonist NBQX (dissolved in dimethylsulfoxide) was compared. Dizocilpine was administered in doses of 0.1 or 0.5 mg/kg, NBQX in doses of 30 or 60 mg/kg, both intraperitoneally 15 min before the first stimulation series. Control siblings were injected with solvens (physiological saline or dimethylsulfoxide, respectively). Each age and dose group was formed by 8-10 rats. Threshold intensities for movements directly elicited by stimulation, spike-and-wave afterdischarges, clonic seizures accompanying these afterdischarges and transition to another type of seizures (limbic type) were evaluated. Both antagonists exhibited only moderate effect on movements directly elicited by stimulation of sensorimotor cortex. In contrast, threshold currents for epileptic afterdischarges of the spike-and-wave type and accompanying clonic seizures were significantly increased by both drugs. The youngest age group was the most sensitive one, the threshold intensities were nearly doubled by higher doses of the two antagonists. Afterdischarges in 25-day-old rats could be suppressed only by dizocilpine. In addition to an increase of threshold intensities, dizocilpine markedly diminished amplitude of spike-and-wave complexes. Threshold for the second type of afterdischarge (limbic type) was increased by dizocilpine but not by NBQX. Our data confirmed high sensitivity of immature brain to excitatory receptor antagonists. The results speak in favor of involvement of both NMDA and nonNMDA receptors in generation of spike-and-wave type of afterdischarges. Only NMDA receptors might play a role in the transition of epileptic activity into limbic structures. (Supported by Center for Neuropsychiatric Studies, project No. LNB00B122.)