Transient impairment of the gabaergic function during initiation of soman-induced seizures.
The changes in extracellular gamma-aminobutyric acid (GABA) levels, the modifications in binding capacities of GABA-receptor subtypes A and B and of the Cl- ionophore sites localized in the ionic-channel associated to the GABAA receptors were studied in hippocampus of rats subjected to a convulsive dose of the acetylcholinesterase inhibitor soman. Whereas extracellular GABA levels, just as binding on GABAA and GABAB receptors, were not modified under soman, a significant transient decrease in the binding capacities of the Cl- ionophore site of the GABAA receptor complex occurred within the first 10 min of seizures in CA1, CA3 areas, and in the dentate gyrus with return to basal values after 30 min. Accordingly, a transient decrease of the brain muscimol-gated Cl- influx was observed after 10 min of seizures. An increased ability of diazepam to potentiate the GABAA gated Cl- influx occurred at the same time. Altogether, these data demonstrated that an impairment of the GABAA receptor function occurs at the beginning of seizures. This suggests that a temporary decrease of GABAAergic function may contribute to the onset of seizures.
Lallement
G
G
Centre de Recherches du Service de Santé des Armées, Unité de Neurotoxicologie, La Tronche, France.
Carpentier
P
P
Pernot-Marino
I
I
Baubichon
D
D
Collet
A
A
Blanchet
G
G
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D012999:Soman / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D012999:Soman; C046308:tert-butylbicyclo-2-benzoate; D003975:Diazepam