Neuroactive steroids that function as positive modulators of
GABA-A receptors are potential
anticonvulsant drugs. We previously demonstrated that
ganaxolone is effective against pentetrazol-induced
motor seizures in immature rats. In the present study, we examined the effects of
ganaxolone in another model, cortical epileptic afterdischarges (ADs). The possible side effects of
ganaxolone were studied in rats 12, 18, and 25 days of age following the implantation of epidural
electrodes. Low-frequency stimulation of the sensorimotor cortical area elicited ADs characterized by a spike-and-wave rhythm and
clonic seizures.
Ganaxolone (5, 10, 20, or 40 mg/kg) was administered intraperitoneally after the first AD and stimulation was repeated five more times. The highest dose of
ganaxolone (40 mg/kg) suppressed progressive prolongation of ADs in 25-day-old rats and postponed it in 12-day-old rats. No significant effect was observed in 18-day-old animals. Movements during stimulation and
clonic seizures accompanying ADs were not affected by
ganaxolone.
Ganaxolone at doses of 20 and 40 mg/kg had no significant effect on motor function, such as surface righting, negative geotaxis, wire mesh ascending, and bar holding. After administration of 40 mg/kg
ganaxolone to 18- and 25-day-old rats, spontaneous locomotion in the open field tended to decrease. Doses of
ganaxolone with a moderate
anticonvulsant effect in the present model did not seriously compromise motor performance.