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Soman-induced convulsions in rats terminated with pharmacological agents after 45 min: neuropathology and cognitive performance.

Myhrer T, Andersen JM, Nguyen NH, Aas P

Norwegian Defence Research Establishment, Protection Division, NO-2027 Kjeller, Norway. trond.myhrer@ffi.no

It has been demonstrated that a triple regimen consisting of procyclidine (6 mg/kg), diazepam (10 mg/kg) and pentobarbital (30 mg/kg) can effectively terminate soman-induced (1 x LD50) seizures/convulsions in rats when administered 30-40 min following onset. However, convulsive activity lasting for only 45 min can result in marked neuronal pathology. The purpose of the present study was to examine potential cognitive impairments of such brain lesions. The results showed that the neuronal pathology (assessed with Fluoro-Jade B) varied from none at all to 30% damage in the index areas (hippocampus, amygdala, piriform cortex). Cognitive deficits were seen in a novelty test (11 days post-exposure) and retention of a brightness discrimination task (28 days post-exposure) among the rats with neuropathology. Furthermore, significant correlations between neuropathology scores and behavioral measures were found for the animals that convulsed. Among these rats, the mortality rate was relatively high (60%) compared with rats in a previous study that had undergone implantation of hippocampal electrodes (17%). Neither the soman poisoning in the absence of convulsions nor the triple regimen alone affected behavior. It is concluded that early management of soman-induced convulsions is of major importance in preventing neuropathology and accompanying cognitive impairments.

Published 5 November 2004 in Neurotoxicology, 26(1): 39-48.
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