The influence of gender on the aggravation of absence seizures by carbamazepine in the low-dose pentylenetetrazol rat model

OBJECTIVES To determine whether carbamazepine (CBZ) aggravates absence seizures in the low-dose pentylenetetrazol (PTZ) rat model in both male and female animals, and investigate for gender differences. METHODS Inbred Sprague-Dawley rats were implanted with EEG electrodes. Seven days later PTZ (20 mg/kg, i.p.) was administered following pre-treatment with vehicle or CBZ (20 mg/kg, i.p.) and the occurrence of spike-and-wave discharges (SWDs) on the EEG quantified. RESULTS The cumulative SWD for 90-minute post-PTZ was higher in the CBZ versus vehicle pre-treatment arm for both female (mean 110 seconds vs. 62 seconds; P = 0.03) and male (mean 89 seconds vs. 60 seconds; P = 0.03) rats. The increase in SWD duration in the CBZ arm was greater in female rats for the first five 15-minute intervals, but none attained statistical significance (P > 0.05). CBZ pre-treatment resulted in reductions in both SWD frequency (Hz) (male, P = 0.003; female, P < 0.0001) and latency to onset of SWD (male, P = 0.002). The frequency of SWD in CBZ pre-treated rats was lower in females (5.8 Hz vs. 6.1 Hz, P = 0.002) as was the decrease in the SWD burst duration following CBZ versus vehicle pre-treatment (-0.05 seconds vs. -0.25 seconds, P = 0.046). CONCLUSIONS CBZ consistently aggravates absence seizures in the low-dose PTZ model in both female and male rats. However, while some gender differences were found, the results failed to support the hypothesis that females are significantly more susceptible to aggravation of the number or duration of absence seizures by CBZ.