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

Epilepsy Res. 1999 Jan;33(1):23-9. doi: 10.1016/s0920-1211(98)00067-9.


Effects of i.p. administration of the neurosteroids, allopregnanolone and pregnenolone sulfate, were studied in WAG/Rij rats, a genetic model for generalized absence epilepsy. EEG recordings showed that allopregnanolone, a positive 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, also increased those parameters, though only at the highest dose used (100 mg/kg). Significant changes in spike-wave discharges occurred during the first hour post-injection and were not accompanied with behavioral alterations. The obtained data indicate that both these neurosteroids aggravate the spike-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Electroencephalography / drug effects
  • Epilepsy, Absence / drug therapy*
  • Epilepsy, Absence / genetics
  • Epilepsy, Absence / physiopathology
  • GABA Modulators / administration & dosage
  • GABA Modulators / pharmacology*
  • Male
  • Pregnanolone / administration & dosage
  • Pregnanolone / pharmacology*
  • Pregnenolone / administration & dosage
  • Pregnenolone / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / drug effects*
  • Receptors, N-Methyl-D-Aspartate / drug effects*


  • Anticonvulsants
  • GABA Modulators
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • Pregnenolone
  • Pregnanolone