Abstracts

RATIONALE: The 6 Hz seizure model is an alternative electroshock paradigm that utilizes a low-frequency, long duration stimulus. The resulting seizure involves a minimal clonic phase followed by stereotyped automatistic behaviors that are similar to the aura of human patients with partial or limbic epilepsy. Levetiracetam which is effective in controlling refractory human partial epilepsies was ineffective against maximal electroshock (MES) and pentylenetetrazol (PTZ) induced seizures, but was effective in blocking seizures in the 6 Hz seizure model, suggesting the utility for this model as a screening tool for partial seizures. To determine which brain structures are involved in the seizure activity of the 6 Hz seizure model, cfos immunohistochemistry was utilized as a marker of seizure-induced neuronal activation. METHODS: Psychomotor seizures were induced in CF-1 mice via corneal stimulation at 6 Hz, 32mA, 0.2ms pulse width and 3 s duration. Results were compared to those obtained following MES (50mA, 0.2 s duration) and intravenous PTZ induced seizures. The mice were sacrificed 2 h after experimental treatment and transcardially perfused with 4% paraformaldehyde. The brains were removed, sliced into 50?M coronal sections and processed for cfos immunohistochemistry. RESULTS: The induction of cfos after 6 Hz stimulation was highest in the caudal region of the amygdala, piriform cortex, and cerebral cortex. No induction of cfos was observed in the hippocampus. Following MES and PTZ-induced seizures, heavy cfos staining was observed in the same areas as well as the dentate gyrus of the hippocampus. CONCLUSIONS: The 6 Hz stimulation results in cfos induction in the cerebral cortex and limited limbic structures. However, unlike MES and PTZ induced seizures, the neuronal activation does not spread to the dentate gyrus of the hippocampus. In this regard, the pattern of cfos induction is clearly different from that observed following MES and PTZ induced seizures. The effect of standard anticonvulsant drugs on neuronal activation as measured by cfos induction is currently being evaluated.