Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice
Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice
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DOI：
10.1073/pnas.95.25.15049
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发表时间：
1998-12-08
影响因子：
11.1
通讯作者：
Tecott, LH
中科院分区：
文献类型：
--
作者：
Heisler, LK;Chu, HM;Tecott, LH
大脑5-羟色胺(5-羟色胺；5-羟色胺)系统是情绪过程的强大调节器，也是治疗精神疾病的药物靶点。为了评价5-HT1A受体对这些过程的调节作用，我们使用基因打靶技术产生了5-HT1A受体突变小鼠，这些动物缺乏功能性的5-HT1A受体，受体放射自显影和抵抗5-HT1A受体激动剂8-羟基-2-(二正丙氨基)四氢萘(8-OH-DPAT)的低温效应，纯合子突变小鼠在旷场、高空迷宫和新对象分析中显示出一致的反应模式，表明焦虑水平上升。此外，它们在尾部悬吊试验中表现出抗抑郁药样反应。这些结果表明，5-HT1a受体基因的靶向性破坏导致了情绪状态的5-羟色胺能调节的可遗传扰动。5-HT1a受体缺失突变小鼠有可能成为研究5-羟色胺能系统调节情感状态和调节精神药物作用的机制的模型。
The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT1A receptor-mutant mice, These animals lack functional 5-HT1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT1A receptor agonist 8-hydroxy-2- (di-n-propylamino)tetralin (8-OH-DPAT), Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs.