Interaction of excitatory amino acid agonists with cortical afterdischarges in developing rats

Abstract

Purpose: To determine the role of excitatory amino acids (EAAs) in genesis of two types of epileptic afterdischarges. Methods: Cortical stimulation and recording electrodes were implanted in 12-, 18-, and 25-day-old rats. Epileptic afterdischarges were induced by rhythmic stimulation of sensorimotor cortex. The stimulation was repeated 6 times with 20-min intervals. Ten minutes after the first afterdischarge, N-methyl-D-aspartate, homocysteine, or kainic acid was injected. The doses were chosen individually for different age groups to be subconvulsive. Type and duration of afterdischarges as well as type and severity of motor correlates were evaluated. Results: N-methyl-D-aspartate prolonged afterdischarges only in 12-day-old rats, whereas two other drugs did it in all age groups. Motor correlates of afterdischarges were changed to flexion seizures in 12-day-old rats after N-methyl-D-aspartate and homocysteine; in 25-day-old rats homocysteine led to generalized tonic-clonic seizures (i.e., both patterns seen after substantially higher doses of these drugs in nonstimulated rats). Seizures lasted tens of minutes. Kainic acid did not change the motor pattern in any age group, but nonconvulsive EEG seizures were recorded in the interstimulation periods mainly in 18- and 25-day-old rats. Increased transition into the limbic type of afterdischarges appeared only after homocysteine in 18- and 25-day-old rats. Conclusions: A mutual potentiation of epileptic phenomena was induced by two agents. The actions of N-methyl-D-aspartate and kainic acid differ in all age groups; the effects of homocysteine were identical with those of N-methyl-D-aspartate in 12-day-old rats but not later. Only homocysteine augmented transition into the limbic type of afterdischarges.