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  • Dynamics of hippocampal acetylcholine release during lithium-pilocarpine-induced status epilepticus in rats.

Dynamics of hippocampal acetylcholine release during lithium-pilocarpine-induced status epilepticus in rats.

Journal of neurochemistry (2014-06-10)
Markus H Hillert, Imran Imran, Martina Zimmermann, Helene Lau, Stefanie Weinfurter, Jochen Klein
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lithium, wire, diam. 3.2 mm, in mineral oil, ≥98%
Sigma-Aldrich
Pilocarpine hydrochloride, ≥99% (titration), powder
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Lithium, granular, 99% trace metals basis
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Lithium, wire (in mineral oil), diam. 3.2 mm, 99.9% trace metals basis
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Lithium, ribbon, thickness × W 0.75 mm × 19 mm, 99.9% trace metals basis
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Lithium, rod, diam. 12.7 mm, 99.9% trace metals basis
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Lithium, ribbon, thickness × W 0.38 mm × 23 mm, 99.9% trace metals basis
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Lithium, ribbon, thickness × W 0.75 mm × 45 mm, 99.9% trace metals basis
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Lithium, ribbon, thickness × W 1.5 mm × 100 mm, 99.9% trace metals basis
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Lithium, granular, 4-10 mesh particle size, high sodium, 99% (metals basis)
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Pilocarpine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Lithium, foil, not light tested, 38x200mm, thickness 0.20mm, as rolled, 99.9%
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Lithium, foil, not light tested, 38x500mm, thickness 0.20mm, as rolled, 99.9%
Lithium, foil, 25x100mm, thickness 0.6mm, as rolled, 99.9%
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Acetylcholine iodide, ≥97%
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USP
Acetylcholine chloride, United States Pharmacopeia (USP) Reference Standard
Acetylcholine chloride, European Pharmacopoeia (EP) Reference Standard