Abstracts

The mechanisms underlying carbamazepine (CBZ) aggravation of absence seizures are uncertain, but are thought to involve enhancement of neuronal activity within the thalamocortical circuitry. We utilised c-Fos immunohistochemistry (cFos-ir) to examine patterns of neuronal activation and the relationship to seizure burden following administration of CBZ to female Generalised Epilepsy Rats of Strasbourg (GAERS). Female ovarectomised GAERS rats implanted with extradural EEG electrodes received, after one week, either 15 mg/kg of CBZ or vehicle i.p. The seizure burden post injection was quantitated by measuring the total duration of spike-wave discharges (SWD), the number and the individual burst length of the discharges over a 90 min EEG recording. Results of the EEG analysis were correlated with cFos-ir in thalamocortical slices. CBZ treated rats (n=5) had significantly greater total duration of SWD vs. vehicle treated rats (n=5) (17.9 vs. 8.8 %, p=0.04). The level of cFos staining did not differ between the treatment groups, however there was a positive correlation between staining intensity in the reticularis thalami (Rt) and both the total seizure duration (r=0.66, p=0.04) and mean burst length (r=0.68, p=0.03), but not with the number of bursts per minute (r=0.13, p=0.71). No significant correlation was found between seizure expression and cFos-ir for any other region examined. The association between increased neuronal activation in the Rt and seizure burden in GAERS provides further support for the critical role of this structure in the generation and maintenance of absence seizures. The lack of difference in cFos activation patterns between CBZ and vehicle treated animals suggests that the mechanism for CBZ aggravation of absence seizures may not involve neuronal activation, but rather enhanced neuronal synchronisation. (Supported by EEG machine provided courtesy of Compumedics, Australia)