Effect of the allopregnanolone and allotetrahydrodeoxycorticosteron on spike-wave discharges in the EEG of absence epilepsy rat models

Abstract

Absence epilepsy is a generalized nonconvulsive type of epilepsy that is characterized by spike-wave discharges (SWD) with a frequency of 2.5-4 Hz in the EEG. The activation of the GABAergic system in central nervous system suppresses convulsive seizures but exacerbates absence seizures. Endogenous neuroactive steroids such as 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THPROG; allopregnanolone) and 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THDOC, allotetrahydrodeoxycorticosteron) are GABA-A receptor-positive allosteric modulators. Finasteride which is a 5 alpha-reductase inhibitor can selectively block the synthesis of endogenous steroids. In this study, we compared the effects of endogenous steroids (THPROG and THDOC) on SWD by using finasteride-treated Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats as a model of absence epilepsy. Wistar (WIS-THPROG and WIS-THDOC) and WAG/Rij (WAG-THPROG and WAG-THDOC) rats were divided into 4 groups (n = 8). After stereotactic surgical procedures, all rats were prepared for direct cortical EEG measurement. Following finasteride administration to each group, THPROG was administered to WIS-THPROG and WAG-THPROG groups, and THDOC to WIS-THDOC and WAG-THDOC groups intraperitoneally. While there was no any SWD activity detected in WIS-THPROG and WIS-THDOC groups, a significant increase in SWD count in WAG-THPROG = 0.012) and in WAG-THDOC (p = 0.012), and in SWD total duration in WAG-THPROG (p = 0.012) and WAG-THDOC groups (p = 0.011) were observed after steroid injection. No difference between the efficacy of THPROG and THDOC on absence seizures in WAG/Rij rats was observed.