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Dynamics of hippocampal acetylcholine release during lithium‐pilocarpine‐induced status epilepticus in rats
Author(s) -
Hillert Markus H.,
Imran Imran,
Zimmermann Martina,
Lau Helene,
Weinfurter Stefanie,
Klein Jochen
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12787
Subject(s) - pilocarpine , status epilepticus , microdialysis , acetylcholine , epilepsy , chemistry , hippocampal formation , medicine , anticonvulsant , endocrinology , epileptogenesis , pharmacology , anesthesia , extracellular , biochemistry , psychiatry
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 AC h 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.), AC h 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 AC h but did not affect seizures, whereas injection of mecamylamine (5 mg/kg i.p.) reduced AC h levels and seizures in a delayed fashion. Local infusion of tetrodotoxin, 1 μM locally) or hemicholinium (10 μM locally) strongly reduced AC h 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 AC h release, and hippocampal AC h 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 AC h, but not glutamate, levels. Treatments that reduce seizure activity also reliably reduce extracellular AC h levels.Status epilepticus was induced in rats by lithium‐pilocarpine administration, and extracellular levels of acetylcholine (ACh) were measured in the hippocampus by microdialysis. Seizures caused several‐fold increases of ACh levels which were reduced to control levels when seizures were stopped by diazepam or ketamine. Further experiments confirmed that cholinergic hyperexcitation accompanies status epilepticus, even when kainate was used as inducing agent.