Sandi C, Venero C, Guaza C
Psychobiology Research Group, Cajal Institute, CSIC, Madrid, Spain.
Eur J Neurosci. 1996 Apr;8(4):794-800. doi: 10.1111/j.1460-9568.1996.tb01264.x.
Glucocorticoids modulate brain function and behaviour through different mechanisms. Although classical effects are mediated through intracellular receptors that modulate gene transcription, recent evidence supports the existence of rapid, nongenomic steroid effects through the neuronal membrane. In this study, we explored possible rapid behavioural effects of corticosterone in the rat, which could provide a model to characterize further the mechanisms involved in rapid corticosteroid nongenomic actions. We found that a corticosterone injection, at doses (2.5 or 5 mg/kg) that mimic plasma concentrations produced by substantial stress, rapidly increases (within 7.5 min of its systemic administration) the locomotor response displayed by rats in a novel environment (activity cage). A lower dose of 1 mg/kg failed to induce this effect. In addition, corticosterone failed to increase locomotion when administered to rats that had been previously exposed to the activity cage. Corticosterone-induced increased locomotion in a novelty situation was not counteracted by either the intracerebroventricular administration of the protein synthesis inhibitor cycloheximide, or by the intracerebroventricular administration of specific antagonists for each type of intracellular corticosteroid receptor, i.e. RU28318, a mineralocorticoid receptor antagonist and RU38486, a glucocorticoid receptor antagonist. Further studies supported the viability of the receptor antagonists to display an anti-corticosteroid action interfering, as previously reported, with the behavioural &winning test. Therefore, the rapid actions of corticosterone in locomotor activity described here, which appear to be nongenomic, might provide a model for future research on the elucidation of the mechanisms involved in steroid-membrane interactions.
糖皮质激素通过不同机制调节脑功能和行为。虽然经典效应是通过调节基因转录的细胞内受体介导的，但最近的证据支持存在通过神经元膜的快速、非基因组类固醇效应。在本研究中，我们探讨了皮质酮在大鼠中可能产生的快速行为效应，这可以为进一步表征快速皮质类固醇非基因组作用所涉及的机制提供一个模型。我们发现，注射剂量为2.5或5mg/kg的皮质酮，模拟由严重应激产生的血浆浓度，在全身给药后7.5分钟内迅速增加（在新环境（活动笼）中大鼠表现出的运动反应）。较低剂量1mg/kg未能诱导这种效应。此外，当给先前暴露于活动笼的大鼠注射皮质酮时，未能增加其运动。在新奇情境中，皮质酮诱导的运动增加，既未被脑室内注射蛋白质合成抑制剂环己酰亚胺所抵消，也未被脑室内注射针对每种细胞内皮质类固醇受体的特异性拮抗剂所抵消，即盐皮质激素受体拮抗剂RU28318和糖皮质激素受体拮抗剂RU38486。进一步的研究支持了受体拮抗剂表现出抗皮质类固醇作用的可行性，如先前报道的那样，可干扰行为“获胜”测试。因此，这里描述的皮质酮在运动活动中的快速作用似乎是非基因组的，可能为未来阐明类固醇-膜相互作用所涉及机制的研究提供一个模型。
