NEUROCHEMICAL MECHANISMS IN SOMAN-INDUCED SEIZURES

This study examined brain regional neurotransmitter level changes as a function of seizure duration following soman intoxication, Rats, impl anted with cortical electrodes and pretreated with HI-6, received a co nvulsant dose of soman, At selected times after seizure onset the EEG recording electrodes were removed and the animal was killed, Spinal co rd 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 ti me of seizure onset. Norepinephrine (NE) levels decreased starting 5 m in after seizure onset and continued to decline, Levels of dopamine (D A) and of its metabolites 3,4-dihydroxyphenylacetic acid and homovanil lic acid were elevated as early as 5 min after seizure onset and there after, The brain levels of aspartate were markedly decreased at and af ter 20 min of seizures; levels of glutamate were depressed at 80 min i n the cortex, Levels of gamma-aminobutyric acid (GABA) were significan tly increased in the cortex starting at 20 min after seizure onset, an d 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 a nd elevation of ACh initiate the seizure process, resulting in seconda ry changes in DA turnover and release of NE, and later changes in exci tatory (aspartate, glutamate) and inhibitory (GABA) amino acid transmi tters. (C) 1997 John Wiley & Sons, Ltd.