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强迫游泳试验中不同小鼠品系在不动行为以及对氟伏沙明和地昔帕明敏感性方面的差异:5-羟色胺和去甲肾上腺素转运体结合分析

Mouse strain differences in immobility and sensitivity to fluvoxamine and desipramine in the forced swimming test: analysis of serotonin and noradrenaline transporter binding.

作者信息

Sugimoto Yumi, Kajiwara Yoshinobu, Hirano Kazufumi, Yamada Shizuo, Tagawa Noriko, Kobayashi Yoshiharu, Hotta Yoshihiro, Yamada Jun

机构信息

Laboratory of Pharmacology, Department of Clinical Pharmacy, Yokohama College of Pharmacy, Matano-cho, Totsuka-ku, Yokohama, 245-0066, Japan.

出版信息

Eur J Pharmacol. 2008 Sep 11;592(1-3):116-22. doi: 10.1016/j.ejphar.2008.07.005. Epub 2008 Jul 10.

Abstract

Strain differences in immobility time in the forced swimming test were investigated in five strains of mice, namely, ICR, ddY, C57BL/6, DBA/2 and BALB/c mice. There were significant strain differences. The immobility times of ICR, ddY and C57BL/6 mice were longer than those of DBA/2 and BALB/c mice. Immobility times were not significantly related to locomotor activity in these strains. There were also differences in sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. In ICR, ddY and C57BL/6 mice, fluvoxamine did not affect immobility time, while it reduced the immobility time of DBA/2 and BALB/c mice dose-dependently. The noradrenaline reuptake inhibitor desipramine decreased immobility time in all strains of mice. Serotonin (5-HT) transporter binding in the brains of all five strains of mice was also investigated. Analysis of 5-HT transporter binding revealed significant strain differences, being lower in DBA/2 and BALB/c mice than in other strains of mice. The amount of 5-HT transporter binding was correlated to baseline immobility time. However, there was no significant relation between noradrenaline transporter binding and immobility time. These results suggest that the duration of baseline immobility depends on the levels of 5-HT transporter binding, leading to apparent strain differences in immobility time in the forced swimming test. Furthermore, differences in 5-HT transporter binding may cause variations in responses to fluvoxamine.

摘要

在五项小鼠实验中研究了强迫游泳试验中不动时间的品系差异,这五项实验分别使用了ICR、ddY、C57BL/6、DBA/2和BALB/c小鼠。品系差异显著。ICR、ddY和C57BL/6小鼠的不动时间比DBA/2和BALB/c小鼠长。这些品系的不动时间与运动活性无显著相关性。对选择性5-羟色胺再摄取抑制剂(SSRI)氟伏沙明的敏感性也存在差异。在ICR、ddY和C57BL/6小鼠中,氟伏沙明不影响不动时间,而在DBA/2和BALB/c小鼠中,它能剂量依赖性地缩短不动时间。去甲肾上腺素再摄取抑制剂地昔帕明可缩短所有品系小鼠的不动时间。还研究了所有五个品系小鼠大脑中的5-羟色胺(5-HT)转运体结合情况。对5-HT转运体结合的分析显示出显著的品系差异,DBA/2和BALB/c小鼠中的结合率低于其他品系小鼠。5-HT转运体结合量与基线不动时间相关。然而,去甲肾上腺素转运体结合与不动时间之间无显著关系。这些结果表明,基线不动的持续时间取决于5-HT转运体结合水平,导致强迫游泳试验中不动时间出现明显的品系差异。此外,5-HT转运体结合的差异可能导致对氟伏沙明反应的变化。

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