Research

Ethosuximide modifies network excitability in the rat entorhinal cortex via an increase in GABA release


Reference:

Greenhill, S. D., Morgan, N. H., Massey, P. V., Woodhall, G. L. and Jones, R. S. G., 2012. Ethosuximide modifies network excitability in the rat entorhinal cortex via an increase in GABA release. Neuropharmacology, 62 (2), pp. 807-814.

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    Official URL:

    http://dx.doi.org/10.1016/j.neuropharm.2011.09.006

    Abstract

    Ethosuximide is the drug of choice for treating generalized absence seizures, but its mechanism of action is still a matter of debate. It has long been thought to act by disrupting a thalamic focus via blockade of T-type channels and, thus, generation of spike–wave activity in thalamocortical pathways. However, there is now good evidence that generalized absence seizures may be initiated at a cortical focus and that ethosuximide may target this focus. In the present study we have looked at the effect ethosuximide on glutamate and GABA release at synapses in the rat entorhinal cortex in vitro, using two experimental approaches. Whole-cell patch-clamp studies revealed an increase in spontaneous GABA release by ethosuximide concurrent with no change in glutamate release. This was reflected in studies that estimated global background inhibition and excitation from intracellularly recorded membrane potential fluctuations, where there was a substantial rise in the ratio of network inhibition to excitation, and a concurrent decrease in excitability of neurones embedded in this network. These studies suggest that, in addition to well-characterised effects on ion channels, ethosuximide may directly elevate synaptic inhibition in the cortex and that this could contribute to its anti-absence effects.

    Details

    Item Type Articles
    CreatorsGreenhill, S. D., Morgan, N. H., Massey, P. V., Woodhall, G. L. and Jones, R. S. G.
    DOI10.1016/j.neuropharm.2011.09.006
    DepartmentsFaculty of Science > Pharmacy & Pharmacology
    Publisher Statementrjones_ehtosux_final_pdf.pdf: NOTICE: this is the author’s version of a work that was accepted for publication in Neuropharmacology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version has been published in Neuropharmacology, vol 62, issue 2, 2012, DOI:10.1016/j.neuropharm.2011.09.006
    RefereedYes
    StatusPublished
    ID Code26936

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