Abstracts

Rationale: Long-term potentiation (LTP) of synaptic transmission 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 doses that exert significant protection against seizures. Lacosamide (LCM) is an AED approved for the adjunctive treatment of partial onset seizures in adults and differentiates from other classic voltage-gated sodium (Na_v) channel blocking AEDs in that it specifically enhances slow inactivation of Na_v channels without affecting fast inactivation. Topiramate (TPM), an AED that induces blockade of Na_v channels among other effects, reportedly affects the cognitive performance of patients receiving chronic treatment. In this study we investigated the effects of LCM and TPM in an in vitro model of LTP induced by tetanic stimulation in the CA1 area of mouse hippocampal slices. Methods: In vitro LTP was recorded in CA1 area from adult C57 black mouse hippocampal slices. Drugs were tested at a final concentration of 100?M. 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 1 second.Results: Basal fEPSP slope was stable and reproducible in the period before TET in LCM- and TPM-treated slices, thus indicating no effect of either drug on basal synaptic transmission. In the LCM- and TPM-treated slices, TET-induced potentiation (LCM: 555% 65%; TPM: 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: LCM: 377% 16%; TPM: 396% 13%, mean SEM) also not different from control group (fitted plateau value: 396% 8%, mean SEM).Conclusions: This study showed that perfusion of 100 ?M LCM or of 100 ?M TPM did not modify LTP recorded in CA1 from mice hippocampal slices. These results suggest that acute treatment with LCM or TPM does not modify neuronal plasticity underlying memory formation in adult mice. Funded by UCB