Elevation and suppression of paraoxon-induced epileptic activity in the rat hippocampus

Background: Organophosphorus cholinesterase inhibitors and an elevated extracellular potassium concentration ([K+]e) elicit clinical epilepsy. We investigated (1) the epilepsy-inducing actions of paraoxon (POX) with elevated [K+]e and (2) the effects of atropine,pralidoxime, and selective muscarinic acetylcholine receptor (mAChR) antagonists on the actions of POX.Materials and Methods: Orthodromically elicited population spikes and fi eld excitatory postsynaptic potentials were simultaneously recorded from the CA1 region in rat hippocampal slices using a multi-electrode array system. Statistics were performed using ANOVA with Bonferroni testing (n = 6).Results: Epileptic activity was elicited in high (7.5, 9.0 mM) [K+]e with or without POX, but not in normal (4.5 mM) [K+]e. The incidence of epileptic activity with POX (83.3%) was signifi cantly higher (p < 0.05) than that without POX in 7.5 mM [K+]e (16.7%). The number of additional population spikes with POX (1.33 ± 1.03) was signifi cantly higher than that prior to and during treatment with atropine (0.16 ± 0.40 and 0.16 ± 0.40, respectively, p < 0.05) or prior to treatment with M1 and M3 mAChR antagonists (0 and 0.16 ± 0.40, respectively, p < 0.05), but not with pralidoxime, M2, or M4 mAChR antagonists in 7.5 mM [K+]e.Conclusion: POX-induced cholinesterase inhibition elicited epileptic activity in elevated [K+]e but not normal [K+]e. Treatment for hyperkalemia likely prevents development of epilepsy following organophosphate intoxication. Atropine, rather than pralidoxime, may be effective at inhibiting organophosphate-induced epileptic activity.