Effects of neurosteroids on spike-wave discharges in the genetic epilepticWAG/Rij rat

Effects of i.p. administration of the neurosteroids, allopregnanolone and p regnenolone sulfate, were studied in WAG/Rij rats, a genetic model for gene ralized absence epilepsy. EEG recordings showed that allopregnanolone, a po sitive modulator of the GABA(A) receptor, in doses ranging from 5 to 20 mg/ kg, increased dose-dependently the number and total duration of spike-wave discharges. Pregnenolone sulfate, a positive modulator of NMDA receptors, a lso increased those parameters, though only at the highest dose used (100 m g/kg). Significant changes in spike-wave discharges occurred during the fir st hour post-injection and were not accompanied with behavioral alterations . The obtained data indicate that both these neurosteroids aggravate the sp ike-wave activity. This finding contrasts with the anti-convulsant effects of some neurosteroids and they point to a different pharmacological profile of epilepsy with convulsive or non-convulsive seizures. (C) 1999 Elsevier Science B.V. All rights reserved.