Triggering of soman-induced seizures in rats: multiparametric analysis with special correlation between enzymatic, neurochemical and electrophysiological data.
Soman, an anticholinesterasic neurotoxic drug, induces epileptic seizures during severe intoxication. The neuropathological lesions then observed are linked to the appearance of these seizures, but their trigger conditions still remain unknown and a great variability between animals is observed. We have developed a technique allowing, in freely moving rats, the in vivo determination of three sets of neurophysiological data, before and during a soman intoxication. For the same rat, we associated cortical acetylcholinesterase (AChE) activity by microdialysis with both the assay of extracellular acetylcholine (ACh) concentrations and electroencephalographic (EEG) recording and power spectrum analysis (gamma band). Data have been analyzed to define the critical parameters which lead to the epileptic fit. Although we found thresholds for seizure occurrence, AChE inhibition having to be over 65% and ACh over 200-fold the baseline, these two criteria are not sufficient to predict the appearance of seizures. Only animals with no increase of energy in the gamma band early after soman poisoning will then exhibit an epileptic fit. Gamma band energy is modulated by noradrenergic activity and might be related to the sympathetic response to stress. So we can hypothesize, that the variation of energy in gamma band after intoxication, which might be related to stress adaptation strategy, may determine whether or not the animal will exhibit an epileptic fit.
Tonduli
L S
LS
Centre de Recherches du Service de Santé des Armées, La Tronche, France. ltonduli@hotmail.com
Testylier
G
G
Marino
I P
IP
Lallement
G
G
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003292:Convulsants / Q000633:toxicity; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D012999:Soman / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D003292:Convulsants; D012999:Soman; D000110:Acetylcholinesterase; D000109:Acetylcholine