Differential effects of phenytoin and sodium valproate on seizure-induced changes in gamma-aminobutyric acid and glutamate release in vivo.
The effects of intraperitoneal administration of the anticonvulsants phenytoin and sodium valproate were compared with ethosuximide on maximal electroshock seizure-related changes in rat hippocampal gamma-aminobutyric acid (GABA) and glutamate release in vivo as measured by microdialysis. There were immediate increases in GABA and glutamate in the 5 min post-ictal period, followed by a sustained reduction in GABA levels. Glutamate levels, however, were subsequently reduced until 20 min post-ictal before gradually increasing above basal. All animals displayed tonic hind-limb extension that was blocked by phenytoin (20 mg/kg) and sodium valproate (400 mg/kg) but not ethosuximide (150 mg/kg). Phenytoin attenuated the immediate post-ictal increase observed in glutamate whilst sodium valproate enhanced GABA release and prevented its secondary post-ictal inhibition. Ethosuximide was without effect on the post-ictal changes. These are the first data to show detailed seizure-induced amino acid changes and the in vivo effects of anticonvulsants on them in the seizure model.
Rowley
H L
HL
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK.
Marsden
C A
CA
Martin
K F
KF
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D010672:Phenytoin