期刊
JOURNAL OF NEUROCHEMISTRY
卷 131, 期 1, 页码 42-52出版社
WILEY
DOI: 10.1111/jnc.12787
关键词
choline; diazepam; kainate; ketamine; microdialysis; seizures
资金
- Goethe University
The lithium-pilocarpine model is a rat model of epilepsy that mimics status epilepticus in humans. Here, we report changes of acetylcholine (ACh) release in the hippocampus before, during and after status epilepticus as monitored by microdialysis in unanesthetized rats. Administration of pilocarpine (30mg/kg s.c.) to rats pretreated with lithium chloride (127mg/kg i.p.) caused a massive, six-fold increase of hippocampal ACh release, paralleling the development of tonic seizures. When seizures were stopped by administration of diazepam (10mg/kg i.p.) or ketamine (75mg/kg i.p.), ACh levels returned to normal. Extracellular concentrations of glutamate remained unchanged during this procedure. Administration of atropine (1mg/kg i.p.) 2h after pilocarpine caused a further increase of ACh but did not affect seizures, whereas injection of mecamylamine (5mg/kg i.p.) reduced ACh levels and seizures in a delayed fashion. Local infusion of tetrodotoxin, 1M locally) or hemicholinium (10M locally) strongly reduced ACh release and had delayed effects on seizures. Administration of glucose or inositol (250mg/kg each i.p.) had no visible consequences. In parallel experiments, lithium-pilocarpine-induced status epilepticus also enhanced striatal ACh release, and hippocampal ACh levels equally increased when status epilepticus was induced by kainate (30mg/kg i.p.). Taken together, our results demonstrate that seizure development in status epilepticus models is accompanied by massive increases of extracellular ACh, but not glutamate, levels. Treatments that reduce seizure activity also reliably reduce extracellular ACh levels.
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