Blockade of "antiabsence" activity of sodium valproate by THIP in rats with petit mal-like seizures. Comparison with ethosuximide.
Wistar rats from our laboratory spontaneously present frequent epileptic seizures whose clinical semeiology, EEG signs and pharmacological reactivity resemble absence seizures in humans. In these rats, GABAmimetics such as THIP enhance the duration of seizures in a dose-dependent fashion. In contrast to the action of these drugs, valproate sodium (VPA), which potentiates GABAergic transmission, abolishes the seizures. VPA injected in association with THIP completely loses its therapeutic effects; moreover, VPA potentiates the aggravating effects of THIP. Ethosuximide which does not interact with GABA, was still effective when given in association with THIP. These findings raise questions as to 1. the role of GABAergic neurotransmission in the occurrence of spontaneous petit-mal-like seizures in the rat, and 2. the mode of action of antiepileptics against these seizures.
D000818:Animals; D004832:Epilepsy, Absence / Q000188:drug therapy*; D005013:Ethosuximide / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D018756:GABA Antagonists; D007267:Injections; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014635:Valproic Acid / Q000037:antagonists & inhibitors* / Q000627:therapeutic use
D018756:GABA Antagonists; D007555:Isoxazoles; D010080:Oxazoles; D005013:Ethosuximide; D014635:Valproic Acid; C015542:gaboxadol