Effects of antiepileptic drugs on afterdischarge generation in rat hippocampal slices.
We have recently reported that ictal-like afterdischarges (ADs) analogous to those in in vivo kindling models are induced by high-frequency stimulation (100 Hz, 1s) to the stratum radiatum of the CA1 region of rat hippocampal slices. To test whether this model can also serve as an in vitro seizure model for temporal lobe epilepsy, we examined the effects of antiepileptic drugs on this model and compared them with their effects on seizures in patients with temporal lobe epilepsy. ADs were progressively enhanced following repetitive high-frequency stimulations to slices treated with 4-aminopyridine, a proconvulsive A-type potassium channel blocker. Bath application of phenytoin (1-100 microM) and carbamazepine (1-100 microM) suppressed AD generation in a concentration-dependent manner. At a clinically relevant concentration of 10 microM, phenytoin reduced the number of spikes in an AD to 50.6% and carbamazepine to 39.7% of the control values. On the other hand, ethosuximide had no effect on AD generation at a concentration of 1 mM, which is clinically effective against absence seizures, but enhanced it at a toxic concentration of 10 mM. These findings indicate that the pharmacological profiles of antiepileptic drugs applied to our model correspond to those applied to seizures in patients with temporal lobe epilepsy. We therefore conclude that this model can be a useful in vitro model for the ictal manifestation of temporal lobe epilepsy.
Ohno
Koji
K
Department of Neuropsychiatry, School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
Higashima
Masato
M
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D002220:Carbamazepine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000503:physiopathology*; D005013:Ethosuximide / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010672:Phenytoin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D018756:GABA Antagonists; D026902:Potassium Channel Blockers; D002220:Carbamazepine; D005013:Ethosuximide; D010672:Phenytoin; D015761:4-Aminopyridine; D001640:Bicuculline