Anti-seizure medication eslicarbazepine affects the synaptic transmission and plasticity in the rat hippocampal synapses

Abstract

Patients with epilepsy often have various memory and cognitive impairments and it has been observed that the use of anti-seizure medications (ASMs) sometimes worsen the conditions. Understanding the mechanism of action of ASMs on neuronal networks is key towards answering the comorbidities of epilepsy. We used single cell patch clamp experiments and field recordings to investigate the mechanism of action of the ASM, eslicarbazepine acetate (ESL) on excitability and synaptic transmission in the hippocampal synapses. Moreover, we also investigated the effect of ESL on long-term potentiation (LTP) in the hippocampal synapses. We found that ESL reduces the neuronal excitability and sodium channel currents in a concentration dependent manner. As a known sodium channel blocker, the application of ESL was expected to decrease the amplitude of fEPSPs, but surprisingly an increase in the amplitude of fEPSPs was observed in the presence of 50 μM and 100 μM ESL (clinically relevant concentrations). This increase in fEPSPs was due to the antagonistic effect of ESL on adenosine A1 receptors. We also studied the effect of ESL on synaptic plasticity and found that 50 μM and 100 μM ESL impaired the LTP in hippocampal synapses. This study shows the interaction of ESL with Adenosine A1 receptors and its effect on synaptic plasticity. This may explain the complex and varied efficacy as well as side effects of ASMs in patients.