Sex differences in sensitivity to seizures elicited by pentylenetetrazol in mice

Sex differences in sensitivity to seizures elicited by intraperitoneally injected pentylenetetrazol (PTZ) were studied in 240 (120 males and 120 females) adult Swiss mice. Animals were separated into four groups according to the dose that was injected: 40, 50, 60 and 70 mg/kg. Seizure severity was expressed by the following scoring scale: (0) no abnormal behavior; (1) myoclonus; (2) running bouncing (RB) clonus; (3) tonic hind limb extension (THE). The analyses of the dose-response curves indicated that females were more susceptible than males when the 50- and 60-mg/kg doses were used. Specifically, females often displayed RB clonus, while males frequently displayed only myoclonus or no abnormal behavior. No significant sex differences were demonstrated when either the 40- or the 70-mg/kg doses were used. These data indicate that, for a specific range of doses, sex differences in seizure susceptibility can be clearly demonstrated with the use of intraperitoneally injected PTZ. In this sense, this method could be used as a tool to investigate the role played by sexual hormones in regulating the sensitivity of the gamma-aminobutiric acid (GABA(A)) receptor complex (GRC).