Sex differences in the response to GABA antagonists depend on the route of drug administration

Sex differences in the responses to two GABA-related convulsants (bicuculline, picrotoxin) were studied in rats and mice following intraperitoneal (i.p.) and intravenous (i.v.) drug administration. Following i.p. administration male and female rats were equally sensitive to bicuculline, while female rats were more sensitive to picrotoxin. After i.v. infusion the threshold doses of bicuculline and picrotoxin producing running/bouncing clonus (RB clonus) were significantly lower in male than in female rats, i.e. male rats were more sensitive to both convulsants than females. Following i.p. administration, at some doses female mice were more sensitive to bicuculline and male mice to picrotoxin, although ED50 values between the sexes were not significantly different. After i.v. infusion, doses of bicuculline producing RB clonus and death were significantly lower in male than in female mice, i.e. male mice were more sensitive to bicuculline. The two sexes of mice were equally sensitive to i.v. administration of picrotoxin. While sex and species differences obtained following i.p. drug administration could presumably be explained by differences in pharmacokinetics, the i.v. route of drug administration is suggested as a reliable technique in the studies of sex and species differences in pharmacodynamics.