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Summary   Objective  Mesial temporal lobe epilepsy ( TLE ) with hippocampal sclerosis is a predominant form of acquired epilepsy, characterized by recurrent simple and complex partial seizures that are often resistant to treatment. Mice developing spontaneous recurrent nonconvulsive and convulsive seizures after intrahippocampal injection of the excitotoxic glutamate agonist kainate are thought to represent a valuable model of mesial  TLE . Epileptic electroencephalogram (EEG) activity recorded in this model from the kainate focus in the ipsilateral hippocampus is resistant to antiseizure drugs such as carbamazepine ( CBZ ). We compared the efficacy of  CBZ  in this model in two different mouse strains ( FVB /N and  NMRI ). Furthermore, we evaluated whether changes in the definition of electrographic seizures affect the antiseizure efficacy of  CBZ .    Methods  As in previous studies, two types of epileptic  EEG  activity were defined: high‐voltage sharp waves ( HVSW s) and hippocampal paroxysmal discharges ( HPD s). The characteristics of these paroxysmal  EEG  events in epileptic mice were compared with  EEG  criteria for nonconvulsive seizures in patients. For  HVSW s, different spike frequencies, interevent intervals, and amplitudes were used as inclusion and exclusion criteria. In addition to  CBZ , some experiments were performed with diazepam ( DZP ) and phenobarbital ( PB ).    Results  Female epileptic  FVB /N mice predominantly exhibited frequent  HVSW s, but only infrequent  HPD s or secondarily generalized convulsive seizures. Slight changes in  HVSW  definition determined whether they were resistant or responsive to  CBZ . Male  NMRI  mice exhibited both  HVSW s and  HPD s.  HVSW s were more resistant than  HPD s to suppression by  CBZ . Both types of epileptic  EEG  activity were rapidly suppressed by  DZP  and  PB .    Significance  The data demonstrate that focal electrographic seizures in the intrahippocampal kainate mouse model are less resistant than previously thought. Both mouse strain and the criteria chosen for definition of  EEG  seizures determine whether such seizures are drug‐resistant or ‐responsive.

The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain