Background: Epilepsy remains challenging to treat still no etiologic treatment has been identified,
however, some antiepileptic drugs (AEDs) are able to modify the pathogenesis of the disease.
Lacosamide (LCM) has been shown to possess complex anticonvulsant and neuroprotective actions,
being an enhancer of the slow inactivation of voltage-gated sodium channels, and it has the potential to
prevent epileptogenesis. Recent evidence has shown that LCM indirectly improves the function of
GABAA receptors. Receptors at most GABAergic synapses involve the gamma-2 subunit, which contributes
to both phasic and tonic inhibition, and its presence assures benzodiazepine sensitivity. Moreover,
mutant gamma-2 subunits were associated with generalized epilepsy syndromes. In animal models,
the expression of the gamma-2 subunit of the gamma-aminobutyric acid A receptor (GABAAg2) was
shown to be increased in pentylenetetrazole (PTZ)-induced chemical kindling in Wistar rats.
Objective: This study hypothesized that LCM might affect the kindling process by influencing the
expression of GABAA receptors in the hippocampus.
Methods: The gene and protein expression levels of the GABAAg2 were studied using RT-qPCR and
Results: It was found that LCM treatment (10 mg/kg i.p. daily for 57 days) reduced the maximal
intensity of the PTZ-induced seizures but did not prevent kindling. On the other hand, LCM treatment
reverted the increase of mRNA expression of GABAAg2 in the hippocampus and prevented the
decrease of GABAAg2 protein in the hippocampal CA1 region.
Conclusion: LCM could exhibit modulatory effects on the GABAergic system of the hippocampus that
may be independent of the anticonvulsant action.