Effect of anti-epileptic drugs in a mouse model of temporal lobe epilepsy Volume 21, issue 2, avril-mai-juin 2009


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SynapCell, bâtiment Biopolis, 5, avenue du Grand-Sablon, 38700 La Tronche, France, Centre de recherche « Grenoble - institut des neurosciences » U836 Inserm-UJF-CEA-CHU, équipe 9 : dynamique des réseaux synchrones épileptiques, bâtiment Edmond-J.-Safra, domaine de la Merci, 38706 La Tronche cedex, France

Both morphological and electroclinical features of human mesial temporal lobe epilepsy (MTLE) have been shown to be mimicked by unilateral injection of kainic acid (KA) in the dorsal hippocampus of adult mice. After an initial status epilepticus and a latent period of two weeks, mice develop spontaneous recurrent hippocampal focal seizures and morphological modifications reminiscent of hippocampal sclerosis. As MTLE is often associated with resistance to anti-epileptic drugs, the pharmacological reactivity to four molecules of epileptic mice was assessed in this study. Only diazepam (0.5-3 mg/kg, i.p.) suppressed hippocampal discharges in a dose- dependent way. Valproate (100-400 mg/kg, i.p.), carbamazepine (25-100 mg/kg, i.p.) and lamotrigine (30-90 mg/kg, i.p.) abolished seizures only at the highest doses. At these doses, EEG activity was strongly impaired and animals showed signs of motor incapacitation. These results show that hippocampal discharges in mice are resistant to classic anti-epileptic drugs and suggest that this model of MTLE constitutes an important tool for the pharmacological evaluation of this form of epilepsy.