Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity:: Application of recombinant adenovirus containing 5-HT1A sequences
Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity:: Application of recombinant adenovirus containing 5-HT1A sequences
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DOI：
10.1523/jneurosci.3223-04.2004
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发表时间：
2004-12-01
影响因子：
5.3
通讯作者：
Garcia, F
中科院分区：
文献类型：
--
作者：
Li, Q;Holmes, A;Garcia, F
我们以前的研究发现，血清素转运蛋白（SERT）基因敲除小鼠表现出对轻微压力的敏感性增加，焦虑样行为增加，但运动活动减少。这些小鼠的下丘脑、杏仁核和中缝背核中的5-羟色胺（5-HT 1A）受体密度也降低。为了评估下丘脑5-HT 1A受体对SERT敲除小鼠的这些表型的贡献，进行了两项研究。用含有5-HT 1A正义和反义序列的重组腺病毒（Ad-1AP-正义和Ad-1AP-反义）操纵下丘脑中的5-HT 1A受体。5-HT 1A基因的表达由5-HT 1A启动子控制，因此它们仅在含有5-HT 1A受体的细胞中表达。(1)将Ad-1AP-正义注射到SERT敲除小鼠的下丘脑中恢复了内侧下丘脑中的5-HT 1A受体;这种效应伴随着消除对盐水注射的过度促肾上腺皮质激素反应（轻微应激）和减少自发活动，但不改变增加的探索性焦虑样行为。(2)为了进一步证实SERT-/-小鼠中的观察结果，将Ad-1AP-反义注射到正常小鼠的下丘脑中。Ad-1AP反义治疗组小鼠下丘脑内侧区5-HT 1A受体密度和功能均明显降低。与对照组（注射Ad-track）相比，Ad-1A-反义治疗的小鼠表现出运动活动的显着减少，但再次没有变化的探索性焦虑样行为，测试高架十字迷宫和旷场测试。因此，本研究结果表明，内侧下丘脑5-HT 1A受体调节应激反应和自发活动，但可能不调节探索性焦虑样行为。
Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1A receptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors.