Restoration of Spike-Wave Discharges after Their Suppression with Ethosuximide in WAG/Rij Rats with Genetic Absence Epilepsy

WAG/Rij rats are a genetic model of absence epilepsy, in which generalized spike-wave discharges (SWDs) are registered on EEG. SWDs are generated in the hyperexcitable somatosensory cortex of the brain. The antiabsence drug ethosuximide (ETX) reduces the excitability of the cortex and, as a result, suppresses SWDs. The work aims to find out the recovery features of discharges after their complete suppression by ETX. To do this, we compared the dynamics of SWD recovery after cancellation of 14-day ETX administration to 7–8-month-old WAG/Rij rats and the age-dependent maturation of SWDs. Earlier, we showed that the age-dependent maturation of discharges goes through 3 stages: 1—immature discharges resembling spindle-like oscillations, 2—immature discharges in which fragments of oscillating activity alternate with fragments of spike-wave complexes, and 3—mature SWDs. During age-dependent maturation of SWDs, mature discharges gradually replace immature ones and, at the same time, spike-wave complexes replace oscillations. After the cancellation of ETX, only immature discharges were present on EEG, among which oscillations prevailed, which corresponds to the 1st stage of age-dependent development of discharges. On the 3rd day after drug cancellation, on EEG immature discharges prevailed, in which oscillations alternate with spike-wave complexes, which corresponds to the 2nd stage of age-dependent development of discharges. On day 7, mature SWDs prevailed, which corresponds to the 3rd stage. Thus, the 3 stages of discharge recovery after ETX cancellation are similar to the stages of age-dependent evolution of SWDs. In the process of discharge restoration, oscillations first appeared, and then waves. Mature discharges replaced immature ones, and spike-wave complexes replaced oscillations. We assume that the restoration of discharges is the result of increased excitability of the somatosensory cortex of the brain after ETX cancellation. Different points of view are discussed regarding the commonality of mechanisms or the independence of the origin of the wave and spike as indispensable attributes of a mature SWD. The results can be used to determine the early stages of spike-wave discharges development for the diagnostics and treatment of patients with absence epilepsy.