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Comparison of Effects of Valproate and Trans ‐2‐en‐Valproate on Different Forms of Epileptiform Activity in Rat Hippocampal and Temporal Cortex Slices
Author(s) -
Sokolova S.,
Schmitz D.,
Zhang C. L.,
Löscher W.,
Heinemann U.
Publication year - 1998
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1998.tb01369.x
Subject(s) - entorhinal cortex , chemistry , hippocampus , hippocampal formation , extracellular , anticonvulsant , epilepsy , cortex (anatomy) , neuroscience , pharmacology , psychology , biochemistry , medicine
Summary:Purpose: Reducing the extracellular magnesium or calcium or increasing the extracellular potassium induces different patterns of epileptiform activity in the hippocampus and the entorhinal cortex. Although in the low Ca 2+ and K + models, seizure‐like events (SLEs) develop in area CA1 of the hippocampus, only short recurrent discharges develop in the low Mg 2+ model. In contrast, in low Mg 2+ , SLEs and late recurrent discharges (LRDs) are observed in the entorhinal cortex. Methods: We compared the effects of valproate (VPA) and its major metabolite, trans ‐2‐en‐VPA (TVPA), on all these different model activities using extracellular field potential measurements. We also investigated the equilibration time course of VPA in the slice by using VPA‐sensitive microelectrodes. Results: Both drugs reversibly blocked most forms of epileptiform activity. The only exception was the LRDs in the entorhinal cortex. In paired experiments, TVPA appeared to be more effective than VPA bath applied with the same concentration to the same slice. With our measurements of the VPA concentrations in slices, we showed that the concentrations used were close to therapeutic drug levels. Conclusions: If TVPA stands the toxicological tests, it might be a useful alternative in the treatment of seizures.