Ethosuximide Affects Paired-Pulse Facilitation in Somatosensory Cortex of WAG\Rij Rats as a Model of Absence Seizure

Abstract

Purpose: The interaction between somatosensory cortex and thalamus via a thalamocortical loop is a theory behind induction of absence epilepsy. Inside peri-oral somatosensory (S1po) and primary somatosensory forelimb (S1fl) regions, excitatory and inhibitory systems are not balanced and GABAergic inhibitory synapses seem to play a fundamental role in short-term plasticity alterations. Methods: We investigated the effects of Ethosuximide on presynaptic changes by utilizing paired-pulse stimulation that was recorded from somatosensory cortex in 18 WAG\Rij rats during epileptic activity. A twisted tripolar electrode including two stimulating electrodes and one recording electrode was implanted into the S1po and S1FL according to stereotaxic landmarks. Paired-pulses (200 µs, 100-1000 µA, 0.1 Hz) were applied to somatosensory cortex at 50, 100, 400, 500 ms inter-pulse intervals for 50 min period. Results: The results showed that paired-pulse facilitation was significantly reduced at all intervals in all times, but compared to the control group of epileptic WAG/Rij rats (p<0.05), it was exceptional about the first 10 minutes after the injection. At the intervals of 50 and 100 ms, a remarkable PPD was found in second, third, fourth and fifth 10-min  post injection. Conclusion: These experiments indicate that Ethosuximide has effects on presynaptic facilitation in somatosensory cortex inhibitory loops by alteration in GABA levels that leads to a markedly diminished PPF in paired-pulse stimulation.

Keywords: Absence seizure, Paired-pulse stimulation, WAG\Rij rat, Somatosensory cortex