未经证实:这项工作是研究自发性高血压大鼠(SHR)中枢5-羟色胺(5-HT)系统的变化及其与SHR行为的相关性。探讨糖皮质激素干预对中枢5-HT系统和SHR行为的影响。
UNASSIGNED:选择三周大的SHR作为注意力缺陷多动障碍(ADHD)模型,并用糖皮质激素受体(GR)激动剂或抑制剂治疗,选择Wista京都大鼠(WKY)作为正常对照组。使用开场测试和Làt迷宫测试来评估自发活动和非选择性注意。采用高效液相色谱法分析大鼠前额叶皮质细胞外液标本中5-HT的含量。GR的表达式,5-HT1A受体(5-HT1AR),和5-HT2A受体(5-HT2AR)在前额叶皮层通过免疫组织化学进行分析。
UNASSIGNED:我们的研究表明,与WKY相比,SHR的前额叶皮层中的5-HT水平较低。开场试验和Làt迷宫试验表明,GR激动剂(地塞米松,DEX)干预改善了注意力缺陷和多动行为,而GR抑制剂(RU486)加重了疾病。有了DEX,5-HT和5-HT2AR在SHR前额叶皮质中的表达水平明显高于对照组,而5-HT1AR的表达水平较低。然而,RU486干预后,5-HT和5-HT2AR的表达水平显着降低,而5-HT1AR的表达水平升高。结果显示,糖皮质激素与5-HT1AR呈负相关,与5-HT2AR呈正相关。
未经证实:在ADHD大鼠的前额叶皮质中,5-HT和5-HT2AR表达的下调和5-HT1AR的上调,与WYK大鼠相比,提示ADHD大鼠中枢5-HT系统功能失调。GR激动剂可上调SHR前额叶皮层5-HT和5-HT2AR的表达,下调5-HT1AR的表达,减轻SHR的多动和注意力缺陷行为。而GR抑制剂则相反。提示ADHD大鼠5-HT系统功能紊乱与糖皮质激素受体活性密切相关。
UNASSIGNED: This work is to investigate the alterations of the central 5-hydroxytryptamine (5-HT) system in spontaneously hypertensive rats (SHR) and the correlation with the behaviors of SHR, and to explore the effects of glucocorticoid intervention on the central 5-HT system and SHR behaviors.
UNASSIGNED: Three weeks old SHR were chosen as the attention-deficit hyperactivity disorder (ADHD) model and treated with glucocorticoid receptor (GR) agonist or inhibitor, whereas Wista Kyoto rats (WKY) were chosen as the normal control group. Open-field test and Làt maze test were used to evaluate the spontaneous activities and non-selective attention. The levels of 5-HT in the extracellular fluid specimens of the prefrontal cortex of rats were analyzed by high-performance liquid chromatography. The expressions of GR, 5-HT1A receptor (5-HT1AR), and 5-HT2A receptor (5-HT2AR) in the prefrontal cortex were analyzed through immunohistochemistry.
UNASSIGNED: Our
study demonstrated that the 5-HT level was lower in the prefrontal cortex of SHR compared to that of WKY. The Open-field test and Làt maze test showed that GR agonist (dexamethasone, DEX) intervention ameliorated attention deficit and hyperactive behavior, whereas GR inhibitor (RU486) aggravated the disorders. With DEX, the expression levels of 5-HT and 5-HT2AR in the prefrontal cortex of SHR were significantly higher than those in the control group, whereas the expression level of 5-HT1AR was lower. However, the expression levels of 5-HT and 5-HT2AR were significantly decreased after the intervention with RU486, while the expression level of 5-HT1AR increased. Results showed that glucocorticoid was negatively correlated with 5-HT1AR and positively correlated with 5-HT2AR.
UNASSIGNED: In the prefrontal cortex of ADHD rats, the down-regulation of 5-HT and 5-HT2AR expressions and the up-regulation of 5-HT1AR, compared with WYK rats, suggested a dysfunctional central 5-HT system in ADHD rats. The GR agonist can upregulate the expression of 5-HT and 5-HT2AR and downregulate the expression of 5-HT1AR in the prefrontal cortex of SHR as well as reduce the hyperactivity and attention deficit behavior in SHR, while the opposite was true for the GR inhibitor. It is suggested that the dysfunction of the 5-HT system in ADHD rats is closely related to glucocorticoid receptor activity.