Abstracts

Rationale: Drug-resistant mesial temporal lobe epilepsy (mTLE), the most common form of focal epilepsy (80%) involves structures of the limbic system such as the hippocampus or the amygdala. Kindling models are accepted as the gold standard in epilepsy research to study the development of seizures,associated neurobiological changes and to identify new drug candidates for mTLE. The model is based on repeated application of electrical stimuli to specific brain regions, such as the amygdala until seizures are elicited. Two common stimulation methods may be used in this model; the application of a constant current stimulation to all animals or a threshold stimulation which is specific to each animal.

The aim of our experiment was to compare the effects of three well-known antiepileptic substances with different mechanisms of action, Carbamazepine, Retigabine and Levetiracetam under both stimulation protocols in the electrical amygdala kindling model.


Methods: Rats were implanted with a depth electrode into the amygdala and surface cortical electrodes. After a recovery period, they were stimulated twice daily with a constant stimulation until exhibiting partial seizures followed by secondary generalization. After selection, half of fully kindled rats were stimulated once daily over two additional weeks with a threshold current stimulation whereas the other half remained stimulated at a constant stimulation.

The rats stimulated with either the constant or threshold stimulation were then alternatively administered one of the three antiepileptic substances with a washout period between each administration. The seizures were scored using the Racine scale and their duration was assessed by EEG.


Results: Antiepileptic effects were observed with Retigabine at 10 mg/kg, regardless of the protocol. Carbamazepine at 500 mg/kg and Levetiracetam at 1000 mg/kg decreased the seizure score and the afterdischarge duration following a threshold stimulation whereas there were no significant effects observed on seizure duration when a constant stimulation was applied.


Conclusions: Both constant and threshold current kindling protocols have their specific advantages and disadvantages. Constant current protocols are less time-consuming and provide reproducible data between animals and experiments. Threshold current protocols may induce seizures which are less difficult to inhibit and may be more suitable for detecting new drug candidates with a moderate effect

Funding: N/A