title: Dynamics of hippocampal acetylcholine release during lithium-pilocarpine-induced status epilepticus in rats.
abstract: 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 (30 mg/kg s.c.) to rats pretreated with lithium chloride (127 mg/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 (10 mg/kg i.p.) or ketamine (75 mg/kg i.p.), ACh levels returned to normal. Extracellular concentrations of glutamate remained unchanged during this procedure. Administration of atropine (1 mg/kg i.p.) 2 h after pilocarpine caused a further increase of ACh but did not affect seizures, whereas injection of mecamylamine (5 mg/kg i.p.) reduced ACh levels and seizures in a delayed fashion. Local infusion of tetrodotoxin, 1 μM locally) or hemicholinium (10 μM locally) strongly reduced ACh release and had delayed effects on seizures. Administration of glucose or inositol (250 mg/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 (30 mg/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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Biocenter N260, Goethe University Frankfurt, Frankfurt am Main, Germany.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Hillert
authors.forename: Imran
authors.initials: I
authors.lastname: Imran
authors.forename: Martina
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Helene
authors.initials: H
authors.lastname: Lau
authors.forename: Stefanie
authors.initials: S
authors.lastname: Weinfurter
authors.forename: Jochen
authors.initials: J
authors.lastname: Klein
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000633:toxicity*; D008297:Male; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D010862:Pilocarpine; D008094:Lithium; D000109:Acetylcholine
keywords: choline; diazepam; kainate; ketamine; microdialysis; seizures