Repeated stress in young and old 5-HT2C receptor knockout mice
Repeated stress in young and old 5-HT2C receptor knockout mice
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DOI：
10.1016/s0031-9384(03)00096-9
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发表时间：
2003-07-01
影响因子：
2.9
通讯作者：
Akana, SF
中科院分区：
文献类型：
--
作者：
Chou-Green, JM;Holscher, TD;Akana, SF
5-羟色胺（5-HT）（2C）受体无效突变（敲除，KO）小鼠发生摄食过多和中年肥胖。基于先前的观察表明这些小鼠对应激环境条件的反应性改变，我们假设该KO小鼠对重复应激反应过度。为了验证这一点，我们研究了两种强度的重复应激对5-HT 2C受体KO和野生型（WT）小鼠的食物摄入量和体重的影响。应激源包括每日换笼（包括处理）3天，然后每日束缚4天。在最后一天，在束缚后立即将小鼠斩首以评估血浆激素水平。使用两个年龄：年轻（12周）和老年（32-34周）。基本上，年轻的KO是prehyperphagic和重量相同的WT。在老年小鼠中，KO明显比WT贪食和重。在响应重复的笼子变化单独，在年轻组的食物摄入量的基因型特异性差异增强，而在老年组，它是减少。这种压力并没有显着影响体重变化或热量效率与年龄或基因型。反复的束缚对幼鼠几乎没有影响。然而，在老年小鼠中，与WT相比，KO的相对体重和热量效率降低。在老年KO小鼠中，与WT小鼠相比，促肾上腺皮质激素（ACTH）、皮质酮和胰岛素增加。总之，这些发现表明5-HT 2C受体KO小鼠对重复应激反应过度，并且这种效应受到应激强度和小鼠初始代谢状态的影响。(C)2003年爱思唯尔科学公司All rights reserved.
Serotonin (5-HT)(2C) receptor null mutant (knockout, KO) mice develop hyperphagia and midlife obesity. Based upon previous observations indicating altered responsiveness to stressful environmental conditions in these mice, we hypothesized that this KO mouse was hyperresponsive to repeated stress. To test this, we examined the effect of two intensities of repeated stress on food intake and body weight in 5-HT2C receptor KO and wild-type (WT) mice. The stressors involved daily cage change (including handling) for 3 days then daily restraint for 4 days. On the final day, mice were immediately decapitated after restraint to assess levels of plasma hormones. Two ages were used: young (12 weeks) and old (32-34 weeks). Basally, young KO were prehyperphagic and weighed the same as WT. In the old mice, KO were frankly hyperphagic and heavier than WT. In response to repeated cage change alone, the genotype-specific difference in food intake in the young group was enhanced, whereas in the old group it was diminished. This stressor did not significantly affect body weight change or caloric efficiency with respect to age or genotype. Repeated restraint had little effect on the young mice. However, in the old mice, KO had decreases in relative body weight and caloric efficiency compared with WT. In the old KO mice, adrenocorticotrophic hormone (ACTH), corticosterone and insulin were increased compared with WT mice. Together, these findings indicate that 5-HT2C receptor KO mice are hyperresponsive to repeated stress and this effect is influenced by stressor intensity and initial metabolic state of the mouse. (C) 2003 Elsevier Science Inc. All rights reserved.