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15–25%), elevations in T-type calcium channel mRNA levels.
doi:10.1016/j.brainres.2004.08.029 
Copyright © 2004 Elsevier B.V. All rights reserved.
Research report
Sensitivity of thalamic GABAergic currents to clonazepam does not differ between control and genetic absence epilepsy rats
Accepted 19 August 2004.
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Abstract
Mutations in GABA-A receptor subunits have been reported in a number of idiopathic generalized epilepsies including childhood absence epilepsy. One of these mutations is located within a high-affinity benzodiazepine-binding domain, and clonazepam is clinically used as an anti-absence drug. The intrathalamic loop consisting of the GABAergic neurons of the nucleus reticularis thalami (NRT) and the thalamocortical (TC) neurons of sensory thalamic nuclei plays an essential role in spike and wave discharges. In a well-established genetic model of absence epilepsy (Genetic Absence Epilepsy rat from Strasbourg, GAERS), systemic injections of benzodiazepines have been shown to suppress spike-and-waves discharges. The aim of this study, therefore, was to determine whether the sensitivity of GABAergic synaptic currents to clonazepam in NRT and TC neurons was different in GAERS and non-epileptic control (NEC) rats. In both pre-seizure GAERS and NEC clonazepam (100 nM) had no effect on the mIPSCs recorded from TC neurons while it increased the decay time constant of the mIPSCs recorded in NRT neurons by a similar amount in GAERS (54.5±5%) and NEC (50.7±5%). Similar results have been obtained in the presence of 100 μM Cd2+, showing that the effect of clonazepam did not occur via modulation of voltage-activated Ca2+ currents. These results are relevant to understand that in GAERS, the clonazepam anti-absence actions cannot be fully explained by the enhancement of the intra-NRT inhibition and the modulation of the GABAergic synaptic currents in other brain areas, in particular the cortex, must be taken into consideration.
Keywords: GABAA receptor; Clonazepam; Thalamus; Epilepsy
Neuroscience classification codes: Disorders of the nervous system, Epilepsy: anticonvulsant drugs
Article Outline
- 1. Introduction
- 2. Methods
- 2.1. Animals
- 2.2. Whole-cell recordings
- 2.3. Drugs
- 2.4. Histological procedures
- 2.5. Statistical analysis
- 3. Results
- 4. Discussion
- Acknowledgements
- References
