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Targeting thalamic nuclei is not sufficient for the full anti-absence action of ethosuximide in a rat model of absence epilepsy

Richards, Douglas A., Manning, Jon-Paul A., Barnes, David, Rombola, Laura, Bowery, Norman G., Caccia, Silvio, Leresche, Nathalie and Crunelli, Vincenzo 2003. Targeting thalamic nuclei is not sufficient for the full anti-absence action of ethosuximide in a rat model of absence epilepsy. Epilepsy Research 54 (2-3) , pp. 97-107. 10.1016/S0920-1211(03)00060-3

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Abstract

Absence epilepsy is characterised by recurrent periods of physical and mental inactivity coupled to bilateral, synchronous spike and wave discharges (SWDs) on the electroencephalogram. The mechanism of action of ethosuximide (ETX), a drug specific for absence seizures, is believed to involve a reduction in the low threshold T-type Ca2+current in thalamocortical and nucleus reticularis thalami (NRT) neurones, although other electrophysiological data have questioned this. Here, we employed a genetic rat model of absence seizures to investigate the effects of directly administering ETX to the thalamus. SWDs were immediately and substantially reduced (∼90%) by systemic administration of ETX (177–709 μmol/kg), or by bilateral microinfusion into the thalamus of the GABABantagonist, CGP 36742 (5–27 nmol per side). However, infusion of ETX (1–200 nmol per side) into the ventrobasal complex or the NRT resulted in a reduction of SWDs that was delayed (30–60 min) and less marked (∼50%). Administration of ETX (0.2 mM to 1 M) to a greater volume of thalamus by reverse microdialysis also produced significant but delayed reduction of SWDs at concentrations >1 mM. Only at 5 mM were seizures significantly reduced (∼70%) within 30 min of administration. These results suggest that targeting of the thalamus alone may be insufficient for an immediate and full anti-absence action for ETX. Concomitant or exclusive actions in the cortex remain a possibility.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Elsevier
ISSN: 0920-1211
Last Modified: 04 Jun 2017 06:30
URI: http://orca.cf.ac.uk/id/eprint/61088

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