Time-dependent changes in rat brain neuroactive steroid concentrations and GABA(A) receptor function after acute stress
Time-dependent changes in rat brain neuroactive steroid concentrations and GABA(A) receptor function after acute stress
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DOI：
10.1159/000126953
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发表时间：
1996-02-01
影响因子：
4.1
通讯作者：
Biggio, G
中科院分区：
文献类型：
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作者：
Barbaccia, ML;Roscetti, G;Biggio, G
在暴露于CO2 1分钟的动物中研究了急性应激引起的大鼠脑神经活性类固醇浓度和γ-氨基丁酸A型（GABA（A））受体功能变化的时间过程，这种治疗已知会诱导大鼠应激和人类恐慌发作。吸入CO2会导致大脑皮质类固醇浓度增加，其时间依赖性因检查的类固醇而异。因此，孕酮和脱氧皮质酮表现出最大的增加（10倍和4倍，分别）10分钟后吸入二氧化碳，并已恢复到基础值分别为30和60分钟。相反，双烯醇酮和3 α-羟基-5 α-双烷-20-酮（别孕烯醇酮）浓度在30分钟时显示出最大增加（分别为+174和+200%），在60分钟时仍高于对照，并在应激后120分钟恢复至对照值。吸入CO2也导致血浆类固醇浓度增加，其中大部分在30分钟达到峰值，并在60分钟时恢复到对照值。通过t-[S-35]丁基双环硫代磷酸酯进行生化评估（[S-35]TBPS）与大脑皮层膜结合或通过Vogel试验中的惩罚反应评分进行行为学检查，结果表明，CO2吸入对这两个参数的影响最大（分别为+51和-40%）;行为反应在60分钟后恢复正常，而[S-35]TBPS结合在应激后120分钟恢复到对照值。结果表明：（a）当冲突行为和[S-35]TBPS结合开始减少时（30分钟），GABA（A）受体的强效和有效正调节剂别孕烯醇酮的脑浓度出现最大增加，和（B）吸入CO2后120分钟，别孕烯醇酮浓度和[S-35]TBPS结合均恢复到对照值。因此，这些数据与神经活性类固醇在应激后恢复GABA能张力中的生理作用一致。
The time courses of changes in rat brain neuroactive steroid concentrations and gamma-aminobutyric acid type A (GABA(A)) receptor function elicited by acute stress were investigated in animals exposed to CO2 for 1 min, a treatment known to induce stress in rats and panic attacks in humans. Inhalation of CO2 induced increases in cerebral cortical steroid concentrations, the time dependence of which varied with the steroid examined. Thus, progesterone and deoxycorticosterone showed maximal increases (10- and 4-fold, respectively) 10 min after CO2 inhalation and had returned to basal values by 30 and 60 min, respectively. In contrast, pregnenolone and 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) concentrations showed maximal increases (+174 and +200%, respectively) at 30 min, were still higher than control at 60 min and returned to control values 120 min after stress. Inhalation of CO2 also resulted in increases in plasma steroid concentrations, most of which peaked at 30 min and had returned to control values by 60 min. A parallel analysis of the stress-induced changes in GABA(A) receptor function, assessed either biochemically by t-[S-35]butylbicyclophosphorothionate ([S-35]TBPS) binding to cerebral cortical membranes or behaviorally by the punished responding score in Vogel's test, showed that the effects of CO2 inhalation on both parameters were maximal(+51 and -40%, respectively) after 10 min; the behavioral reaction returned to normal after 60 min, whereas [S-35]TBPS binding had returned to control values 120 min after stress. The results show that: (a) the maximal increase in the brain concentrations of allopregnanolone, a potent and efficacious positive modulator of GABA(A) receptors, occurred at a time (30 min) when both conflict behavior and [S-35]TBPS binding begun to decrease, and (b) both allopregnanolone concentrations and [S-35]TBPS binding had returned to control values 120 min after CO2 inhalation. The data are thus consistent with a physiological role of neuroactive steroids in restoring GABAergic tone after stress.