Effects of atropine and pralidoxime on neuronal actions of paraoxon in rat hippocampal slices.
The actions of paraoxon, an organophosphorus cholinesterase (ChE) inhibitor, on central synaptic transmission and somatic excitability, and the inhibitory effects of atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, and pralidoxime (PAM), an oxime, on these actions were investigated. From rat hippocampal slices, CA1-population spikes (PSs) and CA1-field excitatory postsynaptic potentials (fEPSPs) at 0.1Hz were recorded using a multi-electrode array (MEA) system. Statistics were performed using ANOVA with Bonferroni/Dunn testing (n=6 in all data). Paraoxon (1μM) depressed fEPSPs but did not significantly influence PSs. The fEPSP depression was inhibited by pre-, simultaneous and post-treatments with atropine (10μM, p<0.01) and pre-treatment with PAM (10μM, p<0.01). The insignificance of the paraoxon-induced PS change was not altered by pre-, simultaneous and post-treatments with atropine or by pre- and post-treatments with PAM; however, PSs were significantly depressed by simultaneous treatment with paraoxon and PAM (p<0.01). Paraoxon-induced ChE inhibition depresses excitatory synaptic transmission and facilitates somatic excitability mediated by mAChRs, and the latter counteracts influence of the depressed synaptic transmission on somatic action potentials. Atropine and PAM prevent and depress the actions of paraoxon and are more effective with earlier treatment.
Narimatsu
Eichi
E
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan. enarimat@sapmed.ac.jp
Niiya
Tomohisa
T
Kawamata
Tomoyuki
T
Kawamata
Mikito
M
Yamakage
Michiaki
M
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009924:Organ Culture Techniques; D010261:Paraoxon / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011220:Pralidoxime Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D011220:Pralidoxime Compounds; D001285:Atropine; C028797:pralidoxime; D010261:Paraoxon