Intracellular recordings were made in an in vitro slice preparation to establish whether the antiepileptic drug topiramate reduces the depolarizing plateau potentials (PPs) induced in the rat subiculum by intracellular pulses of depolarizing current, in the presence of the cholinergic agonist carbachol (CCh, 70–100 μM). PPs lasted up to about 2 s, and disappeared during application of the muscarinic receptor antagonist atropine. Topiramate (10–100 μM, n = 22 neurons) decreased and eventually abolished in a dose-dependent manner these PPs, even when the function of excitatory amino acid and GABAA receptors was blocked. Hence, topiramate depresses muscarinic receptor-dependent PPs in the rat subiculum, thus suggesting that this form of excitation may represent a target for the mechanism of action of this antiepileptic compound.
1Montreal Neurological Institute and Departments of Neurology and Neurosurgery and Physiology, McGill University, 3801 University St, Montréal, Québec, H3A 2B4 Canada
2Centro per l'Epilessia, Ospedale San Paolo, Università degli Studi di Milano, 20142 Milano, Italy
3Corresponding Author: Massimo Avoli
Acknowledgements: This study was supported by the Medical Research Council of Canada (Grant MT-8109), the Savoy Foundation, and a research contract from the R.W. Johnson Pharmacological Research Institute.
Received 28 September 1999; accepted 20 October 1999