Serotonin 5-HT2C receptor knockout mice:: Autoradiographic analysis of multiple serotonin receptors

Serotonin 5-HT2C receptor knockout mice:: Autoradiographic analysis of multiple serotonin receptors
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DOI:
10.1002/jnr.10072
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发表时间:
2002-01-01
影响因子:
4.2
通讯作者:
Vilaró, MT
Vilaró, MT
中科院分区:
医学3区
文献类型:
--
作者:
López-Giménez, JF;Tecott, LH;Vilaró, MT

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应用定量受体放射自显影技术研究了5-HT 2C受体基因敲除小鼠脑内多种5-HT受体亚型和5-HT转运体密度的可能变化。所用的放射性配体为[H-3]西酞普兰、[H-3] WAY 100,635、[H-3]8-OH-DPAT、[H-3] GR 125743、[H-3]舒马曲坦、[H-3] MDL 100,907、[I-125](+/-)DOI、[H-3]美舒麦角碱、[H-3]5-HT、[H-3] GR 113808和[H-3]5-CT。正如预期的那样,标记5-HT 2C的放射性配体。受体显示突变小鼠脉络丛中完全没有标记,并且在表达5-HT 2C受体的其他脑区域中密度显著降低。对于其余的放射性配体,在任何脑区均未发现标记位点密度的显著变化。原位杂交显示5-HT 2A受体和5-羟色胺转运体mRNA水平没有变化,而5-HT 2C受体mRNA水平在某些脑区减少。目前的结果表明,小鼠肾上腺素能系统不表现出补偿性上调或下调的大部分组成部分(5-羟色胺转运蛋白和大多数5-HT受体亚型)在响应于5-HT 2C的情况下。受体。(C)2002 Wiley-Liss,Inc.
Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT2C receptor knockout mice. The radio-ligands employed were [H-3]citalopram, [H-3]WAY100,635, [H-3]8-OH-DPAT, [H-3]GR125743, [H-3]sumatriptan, [H-3]MDL100,907, [I-125](+/-) DOI, [H-3]mesulergine, [H-3]5-HT, [H-3]GR113808, and [H-3]5-CT. As expected, radioligands that label 5-HT2C. receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT2C receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT2A receptor and serotonin transporter mRNA levels, whereas 5-HT2C receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT2C. receptors. (C) 2002 Wiley-Liss, Inc.