Journal article
Antiepileptic drugs and muscarinic receptor-dependent excitation in the rat subiculum
Neuropharmacology, Vol.52(5), pp.1291-1302
04/2007
DOI: 10.1016/j.neuropharm.2007.01.008
PMID: 17337018
Abstract
Field and intracellular recordings were made in an in vitro slice preparation to establish whether the antiepileptic drugs topiramate and lamotrigine modulate cholinergic excitation in the rat subiculum. Bath application of carbachol (CCh, 70–100μM) induced: (i) spontaneous and synchronous field oscillations (duration=up to 7s) that were mirrored by intracellular depolarizations with rhythmic action potential bursts; and (ii) depolarizing plateau potentials (DPPs, duration=up to 2.5s) associated with action potential discharge in response to brief (50–100ms) intracellular depolarizing current pulses. Ionotropic glutamatergic receptor antagonists abolished the field oscillations without influencing DPPs, while atropine (1μM) markedly reduced both types of activity. Topiramate (10–100μM, n=8–13 slices) or lamotrigine (50–400μM, n=3–12) decreased in a dose-dependent manner, and eventually abolished, CCh-induced field oscillations. During topiramate application, these effects were accompanied by marked DPP reduction. When these antiepileptic drugs were tested on DPPs recorded in the presence of CCh+ionotropic glutamatergic and GABA receptor antagonists, only topiramate reduced DPPs (n=5–19/dose; IC50=18μM, n=48). Similar effects were induced by topiramate during metabotropic glutamate receptor antagonism (n=5), which did not influence DPPs. Thus, topiramate and lamotrigine reduce CCh-induced epileptiform synchronization in the rat subiculum but only topiramate is effective in controlling DPPs. We propose that muscarinic receptor-mediated excitation represents a target for the action of some antiepileptic drugs such as topiramate.
Details
- Title: Subtitle
- Antiepileptic drugs and muscarinic receptor-dependent excitation in the rat subiculum
- Creators
- M D'Antuono - Montreal Neurological Institute and Departments of Neurology and Neurosurgery and of Physiology, McGill University, 3801 University Street, Rm. 794, Montréal, H3A 2B4 Québec, CanadaH Kawasaki - Montreal Neurological Institute and Departments of Neurology and Neurosurgery and of Physiology, McGill University, 3801 University Street, Rm. 794, Montréal, H3A 2B4 Québec, CanadaC Palmieri - Montreal Neurological Institute and Departments of Neurology and Neurosurgery and of Physiology, McGill University, 3801 University Street, Rm. 794, Montréal, H3A 2B4 Québec, CanadaG Curia - Montreal Neurological Institute and Departments of Neurology and Neurosurgery and of Physiology, McGill University, 3801 University Street, Rm. 794, Montréal, H3A 2B4 Québec, CanadaG Biagini - Dipartimento di Scienze Biomediche, Università di Modena and Reggio Emilia, 41100 Modena, ItalyM Avoli - Montreal Neurological Institute and Departments of Neurology and Neurosurgery and of Physiology, McGill University, 3801 University Street, Rm. 794, Montréal, H3A 2B4 Québec, Canada
- Resource Type
- Journal article
- Publication Details
- Neuropharmacology, Vol.52(5), pp.1291-1302
- DOI
- 10.1016/j.neuropharm.2007.01.008
- PMID
- 17337018
- NLM abbreviation
- Neuropharmacology
- ISSN
- 0028-3908
- eISSN
- 1873-7064
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 04/2007
- Academic Unit
- Neurosurgery
- Record Identifier
- 9984083285702771
Metrics
33 Record Views