Epilepsy Research (2011) 94, 75—85 journal homepage: www.elsevier.com/locate/epilepsyres Spontaneous epileptiform discharges in a mouse model of Alzheimer’s disease are suppressed by antiepileptic drugs that block sodium channels Sofya Ziyatdinova a,b , Kestutis Gurevicius b , Nino Kutchiashvili a , Tamuna Bolkvadze a , Jari Nissinen a , Heikki Tanila b,c , Asla Pitkänen a,c,* a Epilepsy Research Laboratory, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland b Neurobiology of Memory Laboratory, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland c Department of Neurology, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland Received 26 February 2010; received in revised form 3 January 2011; accepted 8 January 2011 KEYWORDS -Amyloid; Carbamazepine; Phenytoin; Power spectrum; Valproate; Video-EEG Summary Previous studies have demonstrated an increased risk of epilepsy in patients with Alzheimer’s disease (AD). Also, in many mouse models of AD, animals have sponta- neous seizures and frequent epileptiform discharges (EDs). Abnormal function of sodium channels has been proposed to contribute to hyperexcitability in a manner suggesting that drugs that block sodium channels might exacerbate the condition. Here we addressed this question by investigating whether common antiepileptic drugs (AEDs) that block sodium chan- nels, including carbamazepine (CBZ), phenytoin (DPH), or valproic acid (VPA) have any effect on spontaneous seizures or EDs in APdE9 mice. Mice were successively treated with vehi- cle, followed by CBZ (10 mg/kg, t.i.d.), DPH (10 mg/kg, t.i.d.), or VPA (260 mg/kg, b.i.d.) for 3 d. After wash-out and new vehicle treatment, higher doses of CBZ (40 mg/kg, t.i.d.), DPH (40 mg/kg, t.i.d.), or VPA (400 mg/kg, b.i.d.) were administered for 3 d (DPH) or 5 d (CBZ, VPA). During the entire experiment, mice were under continuous (24/7) video-EEG monitoring. Our data show that each treatment reduced the number of spontaneous elec- trographic EDs. VPA was the most effective by reducing the ED frequency below 50% of that at baseline in 75% of mice. Western blot analysis of the Na v 1.1 protein levels in the ventral temporal cortex and the hippocampus did not reveal any differences between the genotypes. Under the conditions tested, sodium channel blocking AEDs suppressed epilep- tiform activity in APdE9 mice with increased amyloid pathology. Whether this applies to ∗ Corresponding author at: A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FIN-70211 Kuopio, Finland. Tel.: +358 50 517 2091; fax: +358 17 163025. E-mail address: asla.pitkanen@uef.fi (A. Pitkänen). 0920-1211/$ — see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2011.01.003