Okuhara D Y, Beck S G
Department of Pharmacology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.
J Pharmacol Exp Ther. 1998 Mar;284(3):1227-33.
Corticosteroids influence neuron activity in the hippocampus through the activation of mineralocorticoid and glucocorticoid receptors. For example, corticosteroids modulate the responses elicited by the activation of several different neurotransmitter receptors on hippocampal pyramidal cells. However, the effects of corticosteroids on the serotonin (5-HT) receptors systems in subfield CA3 are not completely known. Therefore, we used single-electrode voltage clamp techniques to examine the actions of chronic corticosteroid treatment on the 5-HT1A receptor-effector pathway in rat hippocampal subfield CA3 pyramidal cells. Activation of the 5-HT1A receptor increases the conductance of an inward rectifying potassium channel, increasing outward current. The treatment groups used in this investigation were: adrenalectomy, selective mineralcorticoid receptor activation with aldosterone, mineralcorticoid receptor and glucocorticoid receptor activation with high levels of corticosterone and SHAM. Corticosteroids altered the characteristics of the 5-HT concentration-response curve for the 5-HT1A receptor. The effective concentration at 50% of maximum value was smaller in cells from the adrenalectomy treatment group compared to the other treatment groups. The maximum response was smaller in cells from the high corticosterone treatment group compared to SHAM and adrenalectomy treatment group animals. G protein function was also altered by corticosterone treatment. Less current was elicited by guanosine 5'-0-13-thiotriphosphate in cells from the high corticosterone treatment group compared to the other treatment groups and in cells from the SHAM treatment group compared to adrenalectomy treatment group animals. Corticosteroid treatment did not alter the current-voltage relationship, the conductance or the reversal potential of the potassium current linked to the 5-HT1A receptor. We conclude that corticosteroids alter the 5-HT1A receptor-mediated-response in hippocampal subfield CA3 neurons at site(s) downstream of the receptor.
皮质类固醇通过激活盐皮质激素和糖皮质激素受体来影响海马体中的神经元活动。例如，皮质类固醇可调节海马锥体细胞上几种不同神经递质受体激活所引发的反应。然而，皮质类固醇对CA3亚区中5-羟色胺（5-HT）受体系统的影响尚未完全明确。因此，我们采用单电极电压钳技术来研究慢性皮质类固醇处理对大鼠海马CA3亚区锥体细胞中5-HT1A受体 - 效应器途径的作用。5-HT1A受体的激活会增加内向整流钾通道的电导，从而增加外向电流。本研究中使用的处理组包括：肾上腺切除术、用醛固酮选择性激活盐皮质激素受体、用高水平皮质酮激活盐皮质激素受体和糖皮质激素受体以及假手术组。皮质类固醇改变了5-HT1A受体的5-HT浓度 - 反应曲线特征。与其他处理组相比，肾上腺切除术处理组细胞中达到最大反应值50%时的有效浓度更小。与假手术组和肾上腺切除术处理组动物相比，高皮质酮处理组细胞中的最大反应更小。皮质酮处理还改变了G蛋白功能。与其他处理组相比，高皮质酮处理组细胞中鸟苷5'-O-(3-硫代三磷酸)引发的电流更小，且与肾上腺切除术处理组动物相比，假手术组细胞中的电流也更小。皮质类固醇处理并未改变与5-HT1A受体相关的钾电流的电流 - 电压关系、电导或反转电位。我们得出结论，皮质类固醇在受体下游位点改变了海马CA3亚区神经元中5-HT1A受体介导的反应。
