Modulation of 5HT(1A) responsiveness in CA1 pyramidal neurons by in vivo activation of corticosteroid receptors
Modulation of 5HT(1A) responsiveness in CA1 pyramidal neurons by in vivo activation of corticosteroid receptors
复制标题
DOI：
10.1046/j.1365-2826.1996.04724.x
复制
发表时间：
1996-06-01
影响因子：
3.2
通讯作者：
Joels, M
中科院分区：
文献类型：
--
作者：
Hesen, W;Joels, M
在这项研究中，我们描述了在体内激活皮质类固醇受体对大鼠海马CA 1区锥体神经元5 HT反应性的调节作用。在第一系列实验中，肾上腺切除（ADX）大鼠在断头前1小时注射皮质酮（1-1000 μ g/100 g体重），然后通过细胞内记录在体外测定5 HT（1A）诱导的超极化。皮质酮注射对5-HT反应性的影响似乎呈剂量依赖性：当皮质类固醇受体未被激活（ADX）时，5-HT反应相对较大;当盐皮质激素受体（MR）和糖皮质激素受体（GR）均被高剂量皮质酮（100-1000 μ g/100 g体重）注射占据时，观察到类似的5-HT反应。然而，与后一组相比，在接受适量皮质酮（10-30 μ g/100 g）的大鼠切片中，5 HT超极化被显著抑制。接下来，我们研究了血浆皮质酮水平的生理变化是否与递质反应性相关。结果发现，高血浆水平的皮质酮由于压力或外源性应用高剂量的皮质酮与大的5 HT-反应在体外。有趣的是，应激后记录的大的5 HT反应明显被GR拮抗剂RU 38486预处理抑制。总之，这项研究提供了进一步的证据表明，5 HT在海马CA 1区的传输调制的差异类固醇受体激活，可能会发生在生理情况下，由于不同的血浆浓度的皮质酮。
In this study we describe modulatory effects exerted by in vivo activation of corticosteroid receptors on 5HT responsiveness of rat CA1 pyramidal neurons. In the first series of experiments, adrenalectomized (ADX) rats were injected with corticosterone one hour prior to decapitation (1-1000 mu g/100 g body weight) after which 5HT(1A) induced hyperpolarizations were determined in vitro by means of intracellular recordings. It appeared that 5HT responsiveness was dose-dependently affected by corticosterone injections: 5HT responses were relatively large when no corticosteroid receptors were activated (ADX); similar 5HT responses were observed or when both mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) were occupied by injection of high doses of corticosterone (100-1000 mu g/100 g body weight). However, compared to the latter group, 5HT hyperpolarizations were significantly suppressed in slices from rats that received moderate amounts of corticosterone (10-30 mu g/100 g). Next, we investigated whether physiological variations of plasma corticosterone levels as occurring in intact rats correlated with the transmitter responsiveness. It was found that high plasma levels of corticosterone due to either stress or exogenous application of high doses of corticosterone correlated with large 5HT-responses in vitro. Interestingly, the large 5HT responses recorded after stress were clearly suppressed by pretreatment with RU38486, a GR antagonist. Altogether, this study presents further evidence that 5HT transmission in hippocampal CA1 area is modulated by differential steroid receptor activation as may occur under physiological circumstances due to different plasma concentrations of corticosterone.