Abstracts

RATIONALE: Although the aggravation of absence seizures by carbamazepine (CBZ) is well recognized, the underlying pharmacodynamic mechanisms are uncertain. It has been observed clinically in post-pubescent patients this aggravation is more common in females, suggesting an influence of sex hormones. The purpose of this study was to determine whether CBZ aggravates absence seizures in the low-dose pentylenetetrazol (PTZ) rat model in post-pubescent male and female animals, and whether this was influenced by the gender of the animal.
METHODS: Male and female inbred Sprague-Dawley rats were implanted with EEG electrodes under general anaesthesia. After a 7 day recovery peroid, rats were administered PTZ (20 mg/kg, i.p.) following pretreatment with vehicle or CBZ (20 mg/kg, i.p.). The duration of spike-and-wave discharges (SWD) were quantified for six sequential 15 minute intervals post-PTZ administration.
RESULTS: The total cumulative SWD for 90 min post-PTZ was significantly higher in the CBZ vs. vehicle pretreatment arm for both female (mean 110 vs. 62; p=0.03) and male (mean 89 vs. 60 sec; p=0.03) rats. The increase in SWD duration in the CBZ (vs. vehicle) arm was greater in female (vs. male) rats for the first five of the six 15 min intervals following PTZ administration. CBZ pretreatment resulted in significant reductions in both SWD frequency (male p=0.003; female p[lt]0.0001) and latency to onset of SWD (male p=0.002). Additionally, the frequency of SWD in CBZ-pretreated rats was significantly lower in females compared to males (5.8 vs. 6.1 Hz, p=0.02).
CONCLUSIONS: CBZ consistently aggravates absence seizures in the low-dose PTZ model in both female and male post-pubescent rats. Additionally, the results provide evidence of a possible sex difference in the aggravation of SWD by CBZ.
[Supported by: T.J. O[ssquote]Brien was supported by a Viertel Clinical Investigator Grant from the Sylvia and Charles Viertel Charitable Foundation.]