Lacosamide Does Not Alter In Vitro Long-Term Potentiation in Mouse Hippocampal CA1 Area (P05.087)

Abstract

Objective: To investigate the effects of lacosamide and topiramate in an in vitro model of long-term potentiation (LTP) induced by tetanic stimulation in the CA1 area of mouse hippocampal slices. Background Long-term potentiation (LTP) is believed to play an important role in encoding memories in neuronal networks and is a widely accepted model for synaptic plasticity, learning and memory. Several antiepileptic drugs (AEDs) induce memory deficits when tested in preclinical models at therapeutic doses. Lacosamide is an AED that differs from other sodium channel-blocking AEDs such as topiramate by selectively enhancing the slow inactivation of voltage-gated sodium (Nav) channels. Topiramate reportedly affects the cognitive performance of patients receiving chronic treatment. Design/Methods:In vitro LTP was recorded in CA1 area from adult C57 black mouse hippocampal slices. Drugs were tested at a final concentration of 100μM. LTP was studied from field excitatory post-synaptic potentials (fEPSPs) recorded in the stratum radiatum of the CA1 area and evoked by Schaeffer collaterals stimulation. LTP was induced with high frequency stimulation (tetanization; TET) at 100Hz applied once during 1s. Results: Lacosamide and topiramate do not affect basal fEPSP slope, thus indicating no effect of either drug on basal synaptic transmission. In the lacosamide- and topiramate-treated slices, TET-induced potentiation (lacosamide: 555%±65%; topiramate: 599%±53%, mean±SEM) was not different to that in the control group (546%±40%, mean±SEM) and was followed by a subsequent decay to a plateau level (fitted plateau value: lacosamide 377%±16%, topiramate 396%±13%; mean±SEM) also not different from control group (fitted plateau value 396%±8%; mean±SEM). Conclusions: This study showed that perfusion of 100μM lacosamide or of 100μM topiramate did not modify LTP recorded in CA1 from mice hippocampal slices. These results suggest that acute treatment with lacosamide or topiramate does not modify neuronal plasticity underlying memory formation in adult mice. Supported by: UCB Pharma. Disclosure: Dr. Niespodziany has received personal compensation for activities with UCB Pharma as an employee. Dr. Leclegre has received personal compensation for activities with UCB Pharmaceuticals as an employe. Dr. Wolff has received personal compensation for activities with Bial, Eisai Inc., Sepracor and UCB Pharma as a consultant.