Savolainen K M, Muona O, Nelson S R, Samson F E, Pazdernik T L
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Pharmacol Toxicol. 1991 May;68(5):346-54. doi: 10.1111/j.1600-0773.1991.tb01251.x.
Inositol-1-phosphate (Ins1P), an index of phosphoinositide (PI) turnover, was measured in frontal and piriform cortices, caudate, thalamus, hippocampus and cerebellum in saline or LiCl (5 m Eq./kg) pretreated rats 60 min. after graded doses of DFP, paraoxon, or soman. DFP only produced bursts of convulsive activity whereas both paraoxon and soman produced prolonged tonic-clonic convulsions. All three organophosphates (OP) produced convulsions at a lower dose in LiCl than in saline pretreated rats. Regional Ins1P correlated better with the presence or absence of convulsions than with the dose of paraoxon or soman. This was true both in saline and LiCl pretreated rats. In saline pretreated non-convulsing rats, there was a cholinergic increase (1.5-2.0 X) in Ins1P in all brain regions except cerebellum after OP injection. In saline pretreated convulsing rats, there was a marked seizurogenic further increase in Ins1P; highest in caudate (8 X) and cortex (6 X). In LiCl pretreated nonconvulsing rats, the OP-induced cholinergic increase in Ins1P was significant only in caudate, thalamus and hippocampus. In LiCl pretreated convulsing rats, the further seizurogenic increase in Ins1P was less than in saline pretreated rats except in thalamus and hippocampus. Thus, OP produce both a cholinergic and a seizurogenic increase in PI turnover. These data suggest that increased PI turnover in the hippocampus may indicate a lithium-induced lowering of the seizure threshold for OP in limbic regions.
