Pericić D, Manev H, Bujas M
Department of Experimental Biology and Medicine, Ruder Bosković Institute, Zagreb, Croatia.
Brain Res. 1996 Oct 14;736(1-2):174-9. doi: 10.1016/0006-8993(96)00677-4.
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-[3H]butylbicycloorthobenzoate ([3H]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 rats 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.
在幼年和成年雄性及雌性大鼠、接受性腺激素处理的大鼠以及去势的雄性和雌性大鼠中，研究了对GABA阻断剂印防己毒素的敏感性。印防己毒素在引起20日龄雄性和雌性大鼠惊厥方面具有同等效力。成年雌性大鼠往往比幼年大鼠对印防己毒素更敏感，而成年雄性大鼠则比幼年大鼠敏感得多。印防己毒素在取代雄性和雌性大鼠脑粗皮质和小脑膜上的t-[³H]丁基双环邻苯二甲酸酯（[³H]TBOB）结合方面具有同等效力。从30日龄开始对雄性大鼠进行苯甲酸雌二醇的长期处理可增强它们对印防己毒素的敏感性，而对雌性大鼠进行丙酸睾酮的类似处理则无效。成年雄性大鼠去势30天后，印防己毒素诱发惊厥出现的潜伏期缩短，死亡发生率更高。雌性大鼠卵巢切除未能改变对印防己毒素的敏感性。结果表明，性腺激素在大鼠对印防己毒素以及可能对其他与GABA相关药物的反应中性别相关差异的发展中起关键作用。当这种反应性形成时，雄性类型似乎更多地依赖于，而雌性类型则较少依赖于血液中循环激素的存在。
