Effects of gamma-hydroxybutyrate and gamma-butyrolactone derivates on spontaneous generalized non-convulsive seizures in the rat.
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.
Depaulis
A
A
Département de Neurophysiologie et Biologie du Comportement, Centre de Neurochimie du CNRS/INSERM, Strasbourg, France.
Bourguignon
J J
JJ
Marescaux
C
C
Vergnes
M
M
Schmitt
M
M
Micheletti
G
G
Warter
J M
JM
D015107:4-Butyrolactone / Q000494:pharmacology*; D000818:Animals; D004569:Electroencephalography; D004827:Epilepsy / Q000503:physiopathology*; D005663:Furans / Q000494:pharmacology*; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012978:Sodium Oxybate / Q000494:pharmacology*
D005663:Furans; D006885:Hydroxybutyrates; D012978:Sodium Oxybate; D015107:4-Butyrolactone