Rapid glucocorticoid effects on excitatory amino acid levels in the hippocampus: a microdialysis study in freely moving rats
Rapid glucocorticoid effects on excitatory amino acid levels in the hippocampus: a microdialysis study in freely moving rats
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DOI：
10.1046/j.1460-9568.1999.00668.x
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发表时间：
1999-07
影响因子：
3.4
通讯作者：
C. Venero;J. Borrell
中科院分区：
文献类型：
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作者：
C. Venero;J. Borrell
糖皮质激素可以迅速影响哺乳动物的神经功能和行为。一些研究表明，在海马体中可能存在糖皮质激素的快速非基因组效应。为了研究糖皮质激素是否可以通过快速、非基因组机制影响海马区的神经传递，我们研究了急性给予糖皮质激素对海马区CA1区细胞外氨基酸水平的影响。通过对自由活动大鼠的微透析，我们观察到皮质酮(2.5 mg/kg)可引起假手术和肾上腺切除大鼠细胞外天冬氨酸和谷氨酸水平的快速升高(15分钟内)和一过性升高(35-45分钟后恢复到基础水平)(∼为155-160%)。这些影响与皮质酮浓度上升同时发生，这也是通过微透析检测到的，在海马区。海马区逆行透析皮质酮灌流对兴奋性氨基酸(EAA)水平也产生同样快速和可逆的影响。海马区注射糖皮质激素后，细胞外牛磺酸和γ-氨基丁酸浓度无明显变化。这种皮质酮介导的EAA水平的升高不能被这两种细胞内皮质类固醇受体的特异性拮抗剂所抑制，也不能被蛋白质合成抑制剂山奈霉素所抑制。在所有研究病例中，地塞米松(一种合成的糖皮质激素)的灌流引起了与皮质酮治疗相似的效果。然而，非糖皮质激素并不影响该海马区的氨基酸传递。这些结果表明，糖皮质激素在体内诱导了海马区EAA水平的快速和短暂的增加，这可能是通过一种新的非基因组作用机制来发挥作用的。
Glucocorticoids can rapidly affect neuronal function and behaviour in mammals. Several studies have suggested the possible existence of rapid, non‐genomic effects of glucocorticoids in the hippocampus. To investigate whether glucocorticoids could affect neurotransmission in the hippocampus through rapid, non‐genomic mechanisms, we studied the effects of acute glucocorticoid administration on extracellular amino acid levels in the CA1 area of the hippocampus. By means of microdialysis on freely moving rats, we observed that an intraperitoneal injection of corticosterone (2.5 mg/kg) induced a rapid (within 15 min) and transient (returning to basal levels by 35–45 min) increase in extracellular aspartate and glutamate levels (∼ 155–160%), both in sham‐operated and adrenalectomized rats. These effects occurred in parallel with a rise in corticosterone concentration, also detected by microdialysis, in this hippocampal area. Intrahippocampal perfusion of corticosterone by retrodialysis also produced the same fast and reversible effects on excitatory amino acid (EAA) levels. Extracellular concentrations of taurine and γ‐aminobutyric acid (GABA) were unchanged after intrahippocampal glucocorticoid administration. This corticosterone‐mediated rise in EAA levels was not inhibited by the presence of specific antagonists for the two types of intracellular corticosteroid receptors, nor by a protein synthesis inhibitor, anisomycin. Perfusion of dexamethasone, a synthetic glucocorticoid, elicited a similar effect to that observed with corticosterone treatment in all studied cases. However, non‐glucocorticoid steroids did not affect amino acid transmission in this hippocampal area. These results indicate that glucocorticoids induce a rapid and transient increase in hippocampal EAA levels in vivo that might be exerted through a novel non‐genomic mechanism of action.