Neurochemical mechanisms in soman-induced seizures.
This study examined brain regional neurotransmitter level changes as a function of seizure duration following soman intoxication. Rats, implanted with cortical electrodes and pretreated with HI-6, received a convulsant dose of soman. At selected times after seizure onset the EEG recording electrodes were removed and the animal was killed. Spinal cord cholinesterase (ChE) activity was rapidly and maximally depressed, while brain acetylcholine (ACh) levels showed elevations as early as 3 min after soman treatment and reached significantly high levels at time of seizure onset. Norepinephrine (NE) levels decreased starting 5 min after seizure onset and continued to decline. Levels of dopamine (DA) and of its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were elevated as early as 5 min after seizure onset and thereafter. The brain levels of aspartate were markedly decreased at and after 20 min of seizures; levels of glutamate were depressed at 80 min in the cortex. Levels of gamma-aminobutyric acid (GABA) were significantly increased in the cortex starting at 20 min after seizure onset, and in the striatum and hippocampus at 80 min after onset. The levels of glutamine, glycine and taurine were not changed at any time studied. These findings are consistent with the notion that inhibition of ChE and elevation of ACh initiate the seizure process, resulting in secondary changes in DA turnover and release of NE, and later changes in excitatory (aspartate, glutamate) and inhibitory (GABA) amino acid transmitters.
Shih
T M
TM
Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
McDonough
J H
JH
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002395:Catecholamines / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004569:Electroencephalography; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D012999:Soman / Q000633:toxicity*; D013116:Spinal Cord / Q000201:enzymology
D002395:Catecholamines; D002800:Cholinesterase Inhibitors; D018377:Neurotransmitter Agents; D012999:Soman; D000110:Acetylcholinesterase; D000109:Acetylcholine