Paradoxical enhancement of seizures in the gerbil after chronic treatment with sodium valproate.
Handling-induced seizures in male and female gerbils, at 1 year of age, were significantly increased following continuous administration of sodium valproate throughout postnatal life (600 mg/l in drinking fluid of gerbil dams and of the offspring after weaning; 82-111 mg/kg daily). The weight of the brain and gain in body weight of the valproate-treated gerbils were not significantly changed. Three components of the GABAA receptor complex were examined in cerebral cortical tissue from control gerbils and gerbils chronically treated with valproate. No significant differences were found in saturation binding of [35S]-t-butyl-bicyclophosphorothionate or [3H]flunitrazepam, or in the ability of GABA to stimulate the binding of [3H]flunitrazepam. Further studies of this enhancement of susceptibility to seizures are required since it may be of potential clinical relevance.
Cutler
M G
MG
Department of Biological Sciences, Glasgow College of Technology, U.K.
Horton
R W
RW
D000818:Animals; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism; D005849:Gerbillinae; D011963:Receptors, GABA-A / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D014635:Valproic Acid