The sensitivity to the GABA-blocking agent picrotoxin was studied in y
oung and adult male and female rats, in rats treated with gonadal horm
ones and in gonadectomized male and female rats. Picrotoxin was equipo
tent in producing convulsions in male and female 20-day-old rats. Adul
t females tended to be more, while adult males were considerably less
sensitive to picrotoxin than young rats. Picrotoxin was equipotent in
displacing t-[H-3]butylbicycloorthobenzoate ([H-3]TBOB) binding to cru
de cortical and cerebellar membranes from male and female rat brain. C
hronic treatment of male rats, beginning with 30 days of age, with est
radiol benzoate enhanced their sensitivity to picrotoxin, while an ana
logous treatment of female mts with testosterone propionate was ineffe
ctive. Thirty days following castration adult male rats had shorter la
tencies to the appearance of picrotoxin-induced convulsions and a high
er incidence of death. Ovariectomy in females failed to modify the sen
sitivity to picrotoxin. The results suggest that gonadal hormones have
a crucial role in the development of sex related differences in the r
esponse of rats to picrotoxin and presumably to other GABA-related dru
gs. When developed, the male type of reactivity appears to depend more
, and the female type less on the presence of circulating hormones in
the blood.