Sex differences in the effects of gonadectomy and acute swim stress on GABA(A) receptor binding in mouse forebrain membranes

Sex differences in the effects of gonadectomy and acute swim stress on GABA(A) receptor binding in mouse forebrain membranes
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DOI:
10.1016/s0197-0186(96)00143-x
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发表时间:
1997-07-01
影响因子:
4.2
通讯作者:
Johnston, GAR
Johnston, GAR
中科院分区:
医学3区
文献类型:
--
作者:
Akinci, MK;Johnston, GAR

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雄性小鼠的性腺切除导致在GABA浓度为100-1000 nM时前脑膜中GABA(A)受体结合显著增加,而雌性小鼠的性腺切除导致这种结合没有显著变化。在性腺切除的雌性小鼠中,急性游泳应激(在32 ℃下游泳3分钟)导致前脑膜中GABA(A)受体结合的显著增加,GABA浓度为400-1000 nM,血浆皮质酮水平显著增加,而这种应激在性腺切除的雄性小鼠中对这种结合或类固醇水平没有产生显著变化。在GABA浓度为100-1000 nM时,假性腺切除术的手术应激导致两种性别前脑膜中GABA(A)受体结合显着增加,因此未观察到急性游泳应激诱导未手术雌性GABA(A)受体结合增加。在游泳应激、切除性腺的雌性动物中进行的激素替代研究表明,与注射芝麻油溶剂的游泳应激、切除性腺的雌性动物相比,在GABA浓度为100-1000 nM时,腹腔注射雌激素(β-雌二醇,10 μ g)或孕酮(6 α-甲基-17 α-醋酸羟孕酮,1 mg)可显著降低前脑膜中GABA(A)受体结合。注射雌激素(1微克)和黄体酮(0.1毫克)的组合比单独注射任何一种类固醇激素产生了更大的GABA受体结合减少。这些结果表明,除了神经类固醇和皮质类固醇,性腺类固醇有助于调制GABA(A)受体结合的雄性和雌性小鼠的大脑。(C)1997 Elsevier Science Ltd.
Gonadectomy of male mice resulted in a significant increase in GABA(A) receptor binding in forebrain membranes at GABA concentrations of 100-1000 nM, whereas gonadectomy of female mice resulted in no significant change in such binding. Acute swim stress (3 min swim at 32 degrees C) in gonadectomised female mice resulted in a significant increase in GABA(A) receptor binding in forebrain membranes al GABA concentrations of 400-1000 nM and in the plasma levels of corticosterone, whereas this stress produced no significant change in such binding or steroid levels in gonadectomised male mice. The surgical stress of sham gonadectomy produced significant increases in GABA(A) receptor binding in forebrain membranes at GABA concentrations of 100-1000 nM in both sexes, such that the acute swim stress induced increase in GABA(A) receptor binding in unoperated females is not observed. Hormone replacement studies in swim stressed, gonadectomised females indicate that intraperitoneal injection of oestrogen (beta-oestradiol, 10 mu g) or progesterone (6 alpha-methyl-17 alpha-hydroxy-progesterone acetate, 1 mg) significantly decreased GABA(A) receptor binding in forebrain membranes at GABA concentrations of 100-1000 nM compared to swim stressed, gonadectomised females injected with the sesame oil vehicle. The injection of a combination of oestrogen (1 mu g) and progesterone (0.1 mg) produced a greater reduction in GABA, receptor binding than the injection of either steroid hormone alone. These results indicate that, in addition to neurosteroids and corticosteroids, gonadal steroids contribute to the modulation of GABA(A) receptor binding in the brains of male and female mice. (C) 1997 Elsevier Science Ltd.