Calvo N, Martijena I D, Molina V A, Volosin M
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Agencia Postal 4, Casilla de Correo 61, 5000 Córdoba, Argentina.
Brain Res. 1998 Aug 3;800(2):227-35. doi: 10.1016/s0006-8993(98)00515-0.
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 microg/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.
在本研究中，我们检测了甲吡酮（一种皮质酮（CS）合成抑制剂）对短暂束缚所致行为和神经化学后遗症的影响。15分钟的应激期在高架十字迷宫（EPM）中诱发了类似焦虑的行为，在应激事件前3小时注射甲吡酮（75毫克/千克腹腔注射）可逆转此行为。进一步证明，甲吡酮预处理使在暴露于束缚和EPM的动物的大脑皮质组织中观察到的GABA刺激后最大氯化物摄取量的降低恢复正常。此外，在束缚后和EPM暴露后均评估了血浆CS水平。此外，给予CS（2.5毫克/千克皮下注射，剂量模拟束缚诱导的CS水平）或地塞米松（DEXA，1.25微克/千克皮下注射）在EPM中均产生了与束缚诱导的类似的焦虑反应。综上所述，所有这些证据表明，应激反应释放的CS似乎与GABA能超分子复合物的功能变化有关，这可能是暴露于厌恶经历后观察到的焦虑增强的基础。
