Reversible acetylcholinesterase inhibitor donepezil displays prophylactic effects against intoxication with irreversible organophosphorous acetylcholinesterase inhibitors. We used behavioural observation of yawning and epileptic seizures, histochemical acetylcholinesterase staining, and in situ hybridization of the immediate early genes, c-fos and synaptotagmin 4 (Syt4) mRNAs in the brain, to evaluate whether donepezil could protect the brain against the effects of the organophosphate anticholinesterase, diisopropylfluorophosphate, in a rat model of intoxication. Diisopropylfluorophosphatetreated animals exhibited frequent yawning, significant inhibition of acetylcholinesterase staining and upregulation of c-fos mRNA, but not the epileptic seizures or significant change of Syt4 mRNA levels. In order to reduce the threshold for the induction of cholinergic seizures, additional groups of rats were pre-treated with LiCl 24 h before the treatment with diisopropylfluorophosphate. These rats exhibited the seizures, a significant inhibition of acetylcholinesterase staining and significant upregulation of c-fos and Syt4 mRNA levels. All the above-mentioned effects of diisopropylfluorophosphate were inhibited by donepezil pre-treatment. Donepezil pre-treatment by itself induced only a comparatively weaker inhibition of acetylcholinesterase staining and infrequent yawning. We conclude that donepezil protects the brain against diisopropylfluorophosphate-induced effects and that Syt4 mRNA upregulation may serve as a novel marker for organophosphate-induced seizures.

• MeSH
• acetylcholin metabolismus   MeSH
• acetylcholinesterasa metabolismus   účinky léků   MeSH
• antikonvulziva farmakologie   MeSH
• chlorid lithný farmakologie   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• financování organizované MeSH
• geny fos účinky léků   MeSH
• indany farmakologie   MeSH
• isofluorofát farmakologie   MeSH
• krysa rodu rattus MeSH
• messenger RNA genetika   MeSH
• modely u zvířat MeSH
• mozek patologie   MeSH
• piperidiny farmakologie   MeSH
• potkani Wistar MeSH
• receptory cholinergní účinky léků   MeSH
• synaptotagminy genetika   MeSH
• upregulace MeSH
• záchvaty chemicky indukované   patologie   prevence a kontrola   MeSH
• zívání účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH