Serotonin receptor 1A knockout: An animal model of anxiety-related disorder
Serotonin receptor 1A knockout: An animal model of anxiety-related disorder
复制标题
DOI：
10.1073/pnas.95.24.14476
复制
发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Hen, R
中科院分区：
文献类型：
--
作者：
Ramboz, S;Oosting, R;Hen, R
为了研究个体5-羟色胺（5-羟色胺; 5-HT）受体对情绪控制的贡献，我们使用同源重组产生缺乏特异性5-羟色胺能受体亚型的小鼠。在本报告中，我们证明没有5-HT 1A受体的小鼠表现出探索活动减少和对厌恶环境（开放或高架空间）的恐惧增加。5-HT 1A基因敲除小鼠在强迫游泳试验中也表现出不动性降低，这是一种通常与抗抑郁治疗相关的效应。虽然5-HT 1A受体参与控制肾上腺素能神经元的活性，但5-HT 1A敲除小鼠的5-HT和5-羟基吲哚乙酸水平正常，这可能是因为5-HT 1B自身受体的上调。杂合子5-HT 1A突变体表达约一半的野生型受体密度，并在大多数行为测试中显示中间表型。这些结果表明，5-HT 1A受体参与了探索和恐惧相关行为的调节，并表明由于遗传缺陷或环境压力导致的5-HT 1A受体密度降低可能导致焦虑加剧。
To investigate the contribution of individual serotonin (5-hydroxytryptamine; 5-HT) receptors to mood control, we have used homologous recombination to generate mice lacking specific serotonergic receptor subtypes. In the present report, we demonstrate that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces). 5-HT1A knockout mice also exhibited a decreased immobility in the forced swim test, an effect commonly associated with antidepressant treatment. Although 5-HT1A receptors are involved in controlling the activity of serotonergic neurons, 5-HT1A knockout mice had normal levels of 5-HT and 5-hydroxyindoleacetic acid, possibly because of an up-regulation of 5-HT1B autoreceptors. Heterozygote 5-HT1A mutants expressed approximately one-half of wild-type receptor density and displayed intermediate phenotypes in most behavioral tests. These results demonstrate that 5-HT1A receptors are involved in the modulation of exploratory and fear-related behaviors and suggest that reductions in 5-HT1A receptor density due to genetic defects or environmental stressors might result in heightened anxiety.