Gonadal hormones and picrotoxin-induced convulsions in male and female rats

The sensitivity to the GABA-blocking agent picrotoxin was studied in young and adult male and female rats, in rats treated with gonadal hormones and in gonadectomized male and female rats. Picrotoxin was equipotent in producing convulsions in male and female 20-day-old rats. Adult 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 crude cortical and cerebellar membranes from male and female rat brain. Chronic treatment of male rats, beginning with 30 days of age, with estradiol benzoate enhanced their sensitivity to picrotoxin, while an analogous treatment of female mts with testosterone propionate was ineffective. Thirty days following castration adult male rats had shorter latencies to the appearance of picrotoxin-induced convulsions and a higher incidence of death. Ovariectomy in females failed to modify the sensitivity to picrotoxin. The results suggest that gonadal hormones have a crucial role in the development of sex related differences in the response of rats to picrotoxin and presumably to other GABA-related drugs. 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.