Bicuculline-induced rhythmic EEG episodes: Gender differences and the effects of ethosuximide and baclofen treatment

Purpose: There are gender differences in the expression of seizures. We tes ted rhythmic EFG episodes induced by low doses of bicuculline in rats for g ender differences. To verify the validity of these discharges as a model of absence seizures in both male and female rats, we tested the antiabsence d rug ethosuximide (ESM) and a gamma-aminobutyric acid (GABA(B))-receptor ago nist, baclofen, which may exacerbate absence seizures. Methods: Adult rats of both sexes were used. Under general anesthesia, EEG electrodes were implanted over frontal and occipital cortex, and some femal es were ovariectomized. After recovery, male, intact female rats, and femal e rats ovariectomized and ovariectomized rats with estradiol replacement we re compared for occurrence of rhythmic EEG episodes (similar to 6 cycles/s) induced by 2.5 mg/kg of bicuculline, s.c. Because of gender differences in sensitivity to bicuculline, further pharmacologic effects of ESM (125 and 250 mg/kg, i.p.) and baclofen (2 mg/kg, i.p.) were tested separately in mal e (3.0 mg/kg of bicuculline), and female (2.5 mg/kg of bicuculline) rats. Results: After the identical dose of bicuculline, s.c., male and female rat s differed in the incidence of rhythmic episodes and in the latency to onse t of the first as well as the generalized episode. Female rats with natural or exogenous estrogens (but not ovariectomized rats) developed EEG episode s more often than did males, and this effect could be attributed to the pre sence of estrogens. ESM pretreatment suppressed the episodes, whereas baclo fen enhanced their occurrence, as well as the total duration of episodes wi thout gender-specific differences. Conclusions: The study demonstrates gender differences (related probably to the presence of circulating estrogens) in the susceptibility of rats to de velop rhythmic EEG episodes induced by threshold doses of bicuculline. This activity has some features of an acute absence seizure model.