Effects of gamma-hydroxybutyrate and gamma-butyrolactone derivates on spontaneous generalized non-convulsive seizures in the rat

Neuropharmacology. 1988 Jul;27(7):683-9. doi: 10.1016/0028-3908(88)90076-7.

Abstract

The effects of derivatives of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone were examined in Wistar rats from a strain in which spontaneous spike-and-wave discharges can be recorded electroencephalographically. For each compound, the effects were compared to those obtained in rats from a strain without spontaneous seizures. Administration of GHB (62.5-375 mg/kg, i.p.) increased, in a dose-dependent manner, the duration of spontaneous spike-and-wave discharges. In non-epileptic rats, this compound (250 and 375 mg/kg) induced bursts of spikes of a lower frequency and smaller amplitude than spontaneous spike-and-wave discharges. Similar results were obtained in both strains, respectively, after injection of gamma-butyrolactone (85-170 mg/kg, i.p.). This latter compound, however, showed greater potency in its epileptogenic effects than GHB. Administration of trans gamma-hydroxycrotonic acid (up to 1000 mg/kg, i.p.), a semi-rigid analogue of GHB was without any effect in both strains of rats. Injection of gamma-crotonolactone (42.5-170 mg/kg, i.p.), suppressed the spike-and-wave discharges in epileptic rats and had no effect in non-epileptic animals. These results confirm the similarities between seizures induced by GHB and spontaneous spike-and-wave discharges in the rat. The neural mechanism of the epileptogenic effect of GHB is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / pharmacology*
  • Animals
  • Electroencephalography
  • Epilepsy / physiopathology*
  • Furans / pharmacology*
  • Hydroxybutyrates / pharmacology*
  • Male
  • Rats
  • Rats, Inbred Strains
  • Sodium Oxybate / pharmacology*

Substances

  • Furans
  • Hydroxybutyrates
  • Sodium Oxybate
  • 4-Butyrolactone