Pericić D, Svob D, Jazvinsćak M, Mirković K
Laboratory for Molecular Neuropharmacology, Ruder Bosković Institute,Bijenićka c. 54, P.O.B. 1016, 10000 Zagreb, Croatia.
Pharmacol Biochem Behav. 2000 Aug;66(4):879-86. doi: 10.1016/s0091-3057(00)00267-7.
To explore the possible involvement of glucocorticoids in the previously observed anticonvulsive effect of swim stress, mice were, prior to administration of convulsants, subjected to treatments that diminish or enhance plasma corticosterone levels. Aminoglutethimide, the inhibitor of steroid synthesis, failed to modify convulsant doses of picrotoxin, but enhanced threshold doses of pentylenetetrazole producing myoclonus and death, both in unstressed and stressed animals. The same drug prevented the effect of stress on pentylenetetrazole-induced running bouncing clonus (RB clonus) and abolished the appearance of tonic hindlimb extension (THE). Doses of kainic acid producing convulsions and death were not affected by stress, but they were enhanced by aminoglutethimide. Corticosterone administration could not imitate the effect of swim stress. Finasteride, a 5 alpha-reductase inhibitor, did not interfere with the effect of stress on picrotoxin-induced convulsions. Swim stress failed to modify the binding of the convulsant t[3H]-butylbicycloorthobenzoate [3H]TBOB, to washed mouse forebrain membranes. The results confirmed an anticonvulsant effect of swim stress against convulsions produced by GABA-related convulsants, but they do not support the hypothesis suggesting the involvement of glucocorticoids or neurosteroids in this effect.
为探究糖皮质激素是否可能参与先前观察到的游泳应激的抗惊厥作用，在给予惊厥剂之前，对小鼠进行处理以降低或提高血浆皮质酮水平。氨基导眠能作为类固醇合成抑制剂，未能改变苦味毒的惊厥剂量，但在未应激和应激的动物中，均提高了戊四氮产生肌阵挛和死亡的阈值剂量。同一药物可防止应激对戊四氮诱发的奔跑弹跳阵挛（RB阵挛）的影响，并消除强直性后肢伸展（THE）的出现。产生惊厥和死亡的 kainic 酸剂量不受应激影响，但氨基导眠能可使其增加。给予皮质酮无法模拟游泳应激的效果。非那雄胺作为一种 5α-还原酶抑制剂，不干扰应激对苦味毒诱发惊厥的影响。游泳应激未能改变惊厥剂[3H]-叔丁基双环邻苯二甲酸酯（[3H]TBOB）与洗涤过的小鼠前脑细胞膜的结合。结果证实了游泳应激对 GABA 相关惊厥剂诱发惊厥具有抗惊厥作用，但不支持糖皮质激素或神经甾体参与此作用的假说。
