The aim of this study was to investigate if p-chloroamphetamine (PCA), which is neurotoxic to serotonin (5-HT) nerve terminals, was able to induce, like 3,4-methylenedioxymethamphetamine, a region-specific regulation of 5-HT1A receptor mRNA expression. The effect of PCA on the expression of 5-HT7 receptors, which share some pharmacological properties with 5-HT1A receptors, was comparatively studied. PCA (2 x 5 mg/kg) produced a lasting depletion of 5-HT content in the rat frontal cortex and hippocampus. In the hippocampus, the maximal 5-HT depletion was found on day 21 (-70%), whereas in the cortex, the highest 5-HT depletion was found on day 14 (-73%), with a partial but significant recovery on day 21. At the latter time point, 5-HT1A receptor mRNA expression was increased by 80% in the cortex and decreased by 50% in the hippocampus. The 5-HT1A receptor mRNA expression was also enhanced after exposure to PCA of rat cortical but not of hippocampal primary cultures. In regard to 5-HT7 receptor mRNA expression, the most remarkable change after PCA was the great increase (+200%) in the brain-stem. Binding studies to 5-HT1A receptors matched the changes in receptor mRNA expression. Gel shift assays revealed enhanced nuclear protein binding to the KB sequence with use of cortical but not hippocampal extracts of PCA-treated rats. Overall, the data show region-specific changes in 5-HT receptor-type expression that may not be entirely dependent on the neurotoxic effect of PCA on 5-HT terminals.

译文

这项研究的目的是研究对5-羟色胺 (5-HT) 神经末梢具有神经毒性的对氯苯丙胺 (PCA) 是否能够像3,4-亚甲二氧甲基苯丙胺一样诱导5-HT1A受体mRNA表达。比较研究了PCA对5-HT7受体表达的影响,该受体与5-HT1A受体具有某些药理特性。PCA (2x5 mg/kg) 在大鼠额叶皮层和海马中持续消耗5-HT含量。在海马中,最大的5-HT耗竭在第21天 (-70%) 发现,而在皮质中,最高的5-HT耗竭在第14天 (-73%) 发现,在第21天部分但显着恢复。在后一个时间点,5-HT1A受体mRNA的表达在皮层中80% 增加,而在海马中50% 减少。暴露于大鼠皮质的PCA而不是海马原代培养物后,5-HT1A受体mRNA的表达也得到了增强。关于5-HT7受体mRNA表达,PCA后最显着的变化是脑干中的显着增加 (200%)。与5-HT1A受体的结合研究与受体mRNA表达的变化相匹配。凝胶位移测定显示,使用PCA处理的大鼠的皮质而不是海马提取物,核蛋白与KB序列的结合增强。总体而言,数据显示5-HT受体类型表达的区域特异性变化可能不完全取决于PCA对5-HT末端的神经毒性作用。

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