title: Evidence that changes in levels of cyclic nucleotides in the CNS are not related to soman-induced convulsions.
abstract: Others have suggested that organophosphate-induced convulsions are related to changes in levels of cyclic nucleotides, especially in cerebella. We have examined this question by subcutaneously injecting male Sprague-Dawley rats (approx 250-300 gm) with three different doses of soman: a subconvulsive dose of 40 micrograms/kg, a convulsive dose of 120 micrograms/kg (which is approx 90% of the ED50 for convulsions) and a higher convulsive dose of 150 micrograms/kg. The incidence and severity of convulsions were monitored until the rats were sacrificed by focused microwave irradiation of the head at the following times after injections: 4 min, 10 min, 1 hr and 6 hr, which represent times prior to onset of convulsions, at onset of convulsions, at peak convulsive activity and during recovery from convulsions, respectively. Results showed that in rat striata, cerebella and thoracic spinal cord, neither changes in levels of cyclic AMP and cyclic GMP nor changes in ratios of cyclic AMP to cyclic GMP were correlated with soman-induced convulsions, i.e., none of the changes in cyclic AMP and cyclic GMP and/or in the ratios of cyclic AMP to cyclic GMP were related to the initiation of, maintenance of, or recovery from soman-induced convulsions.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
authors.forename: D D
authors.initials: DD
authors.lastname: Liu
authors.forename: E
authors.initials: E
authors.lastname: Ueno
authors.forename: I K
authors.initials: IK
authors.lastname: Ho
authors.forename: B
authors.initials: B
authors.lastname: Hoskins
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D012999:Soman / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D012999:Soman; D000242:Cyclic AMP; D006152:Cyclic GMP