Metyrapone pretreatment prevents the behavioral and neurochemical sequelae induced by stress
Metyrapone pretreatment prevents the behavioral and neurochemical sequelae induced by stress
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DOI：
10.1016/s0006-8993(98)00515-0
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发表时间：
1998-08-03
期刊：
影响因子：
2.9
通讯作者：
Volosin, M
中科院分区：
文献类型：
--
作者：
Calvo, N;Martijena, ID;Volosin, M
在这项研究中，我们研究了皮质酮(CS)合成的抑制剂美替拉酮对短暂束缚所引起的行为和神经化学后遗症的影响。应激期15min后，高架正迷宫(EPM)上出现类焦虑行为，而美替拉酮(75 mg/kg，i.p)可逆转这一行为。在应激事件前3小时注射。进一步证明，在同时暴露于束缚和EPM的动物的大脑皮层组织中，观察到GABA刺激后最大氯离子摄取量的下降，美替拉酮的预处理可使其正常化。此外，还评估了束缚后和EPM暴露后的血浆CS水平。此外，两种CS(2.5 mg/kg S.C.地塞米松(1.25微克/千克体重皮下注射)或地塞米松(1.25微克/千克体重皮下注射)在EPM引起的焦虑反应与束缚引起的焦虑反应相当。综上所述，所有这些证据表明，应激时释放的CS似乎与GABA能超分子复合体的功能变化有关，这可能是暴露在厌恶经历后观察到的增强焦虑的基础。(C)1998 Elsevier Science B.V.保留所有权利。
In the present study, we examined the effect of metyrapone, an inhibitor of corticosterone (CS) synthesis, on the behavioral and neurochemical sequelae induced by a brief restraint session. A 15-min stress period induced an anxiogenic-like behavior on the elevated plus-maze (EPM), which was reversed with metyrapone (75 mg/kg i.p.) injected 3 h prior to the stress event. It was further demonstrated that metyrapone pretreatment normalized the decrease in maximal chloride uptake following GABA stimulation observed in brain cortex tissue obtained from animals exposed to both restraint and the EPM. In addition, plasma CS levels were assessed both after restraint and following EPM exposure. Furthermore, the administration of both CS (2.5 mg/kg s.c. at a dose that mimics CS levels induced by restraint) or dexamethasone (DEXA, 1.25 mu g/kg s.c) resulted in an anxiogenic response in the EPM comparable to that induced by restraint. Taken together, all these evidence suggest that CS released in response to stress seems to be associated with functional changes at the GABAergic supramolecular complex which could underlie the enhanced anxiety observed following the exposure to an aversive experience. (C) 1998 Elsevier Science B.V. All rights reserved.