Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor
Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor
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DOI：
10.1016/j.physbeh.2004.01.018
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发表时间：
2004-06-01
影响因子：
2.9
通讯作者：
Dallman, MF
中科院分区：
文献类型：
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作者：
Bhatnagar, S;Sun, LM;Dallman, MF
5-羟色胺-3（5-HT-3A）受体定位于边缘系统和脑干结构，调节焦虑相关行为和下丘脑-垂体-肾上腺（HPA）活性，但其在调节焦虑相关行为中的作用是不明确的，其在调节HPA活性中的作用的证据有限。因此，我们使用5-HT-3A受体敲除（KO）小鼠来进一步研究这些问题。除了基础和急性应激条件下的HPA活性外，还检查了高架十字迷宫、旷场、明暗箱和巴甫洛夫恐惧条件反射后的行为。与年龄匹配的成年雄性野生型（WT）对照组相比，成年雄性KO小鼠在高架十字迷宫的开放肛门中行进的距离增加，与焦虑测量值降低一致。两种基因型在旷场和光暗实验中的探索行为没有差异。KO小鼠表现出增强的恐惧条件反射，其指数为恐惧诱导的冻结行为。KO小鼠表现出较低的促肾上腺皮质激素（ACTH）反应的限制或脂多糖（LPS）。此外，与WT小鼠相比，KO小鼠下丘脑室旁核（PVN）中的加压素mRNA较低，中央杏仁核中的促肾上腺皮质激素释放激素（CRH）mRNA较高。因此，5-HT-3A受体的缺失揭示了该受体在调节HPA对急性应激的反应中的重要作用，以及杏仁核中5-HT-3A受体与CRH之间的潜在相互作用。总之，这些数据表明，5-HT-3A受体在焦虑和恐惧相关行为的调节中没有单一的作用，但在HPA活性的调节中具有潜在的实质性作用。(C)2004年爱思唯尔公司All rights reserved.
The serotonin-3 (5-HT-3A) receptor has been localized in limbic and brainstem structures that regulate anxiety-related behavior and hypothalamic-pituitary-adrenal (HPA) activity, but its role in regulating anxiety-related behaviors is equivocal, and evidence for its role in regulating HPA activity is limited. Therefore, we used 5-HT-3A receptor knockout (KO) mice to further study these issues. Behavior in the elevated plus maze, open field, light-dark box and after Pavlovian fear conditioning was examined in addition to HPA activity under basal and acute stress conditions. Compared to age-matched adult mate wild-type (WT) controls, adult male KO mice exhibited increased distance traveled in the open anus of the elevated plus maze, consistent with decreased measures of anxiety. There were no differences between the two genotypes in exploratory behavior in the open field or light-dark test. KO mice displayed enhanced fear conditioning indexed by fear-induced freezing behavior. KO mice displayed lower adrenocorticotropin (ACTH) responses to restraint or lipopolysaccharide (LPS). In addition, lower vasopressin mRNA in the paraventricular nucleus of the hypothalamus (PVN) and higher corticotropin-releasing hormone (CRH) mRNA in the central amygdala were observed in KO compared to WT mice. Therefore, deletion of the 5-HT-3A receptor revealed an important role for this receptor in regulating HPA responses to acute stress and a potential interaction between the 5-HT-3A receptor and CRH in the amygdala. Together, these data suggest that the 5-HT-3A receptor does not have a unitary role in the regulation of anxiety- and fear-related behaviors but has a potentially substantial role in the regulation of HPA activity. (C) 2004 Elsevier Inc. All rights reserved.