Gender difference in susceptibility to picrotoxin-induced seizures is seizure- and stimulation-dependent

In a dose-response study, the pattern of sex-associated susceptibility to picrotoxin-induced myoclonic, focal, akinetic, and generalized tonic-clonic (GTC) seizures was investigated in rats to determine whether the reported heightened susceptibility of females to seizures was a general phenomenon in rats or whether it was limited to specific types of seizures. The latency to and incidence of specifically categorized seizures were used as indices of susceptibility after male and female rats had been injected with picrotoxin (3-10 mg/kg). The results revealed that at low doses of picrotoxin (4 mg/kg), female rats had significantly shorter latencies to myoclonic seizures and significantly shorter latencies and higher incidences of GTC seizures. At higher doses of picrotoxin (8 and 10 mg/kg), the pattern of relative susceptibility of males and females to myoclonic seizures was reversed, with males having shorter latencies than females. There were no significant sex differences in the incidence of or latency to focal or akinetic seizures at any of the doses tested. These findings indicate 1) that there are significant sex differences in seizure susceptibility only for specific seizure categories in rats; and 2) that for seizure categories where significant sex differences were identified, the observed pattern of relative susceptibility of males and females depends on the dose of picrotoxin tested. Thus, patterns of sex-associated seizure susceptibility favoring either males or females are both seizure- and stimulation-limited and do not reflect general dispositions to seizures in either sex.(ABSTRACT TRUNCATED AT 250 WORDS)