Multifaceted strain-specific effects in a mouse model of depression and of antidepressant reversal
Multifaceted strain-specific effects in a mouse model of depression and of antidepressant reversal
复制标题
DOI：
10.1016/j.psyneuen.2008.07.010
复制
发表时间：
2008-11-01
影响因子：
3.7
通讯作者：
Belzung, Catherine
中科院分区：
文献类型：
--
作者：
Ibarguen-Vargas, Yadira;Surget, Alexandre;Belzung, Catherine
抑郁症的发病机制和对治疗不敏感的原因仍然知之甚少，尽管基因构成已被确定为一个促成因素。近交系小鼠的同源性为研究基因与行为或药物反应之间的联系提供了有用的工具。因此，我们的目的是鉴定对9周不可预测的慢性轻度应激（UCMS）敏感的自交系小鼠（A /J、BALB/c、C3H、C57BL/6、CBA、DBA和FVB），以及从第5周开始，抗抑郁药（丙咪胺，20 mg/kg/天i.p）对各种抑郁相关变化（身体、行为和神经内分泌状态）的逆转作用。UCMS显著降低了所有菌株的皮毛状态，降低了新颖性抑制饲养（NSF）试验中的情绪反应（a /J, BALB/c, C57BL/6），并改变了粪便皮质酮代谢物（BALB/c, C57BL/6， DBA， FVB）水平。丙咪嗪治疗逆转了ucms诱导的皮毛状态（BALB/c， DBA）、NSF测试（A/J, BALB/c, C57BL/6）和粪便皮质酮代谢物（BALB/c, C57BL/6）的改变。C3H、CBA和FVB小鼠对丙咪嗪治疗无反应。值得注意的是，在某些菌株（A/J, C3H， CBA）中，ucms诱导的身体或行为改变没有发生下丘脑-垂体-肾上腺（HPA）轴的改变，尽管ad诱导的BALB/c和C57BL/6的这些变化逆转与HPA轴正常化有关。最后，研究表明，UCMS能够区分各种改变，并以菌株依赖的方式复制与人类疾病亚型相似的多种特征。因此，UCMS可以选择适合研究特定抑郁症相关特征的菌株，并可能成为识别与易感性增加、情感障碍的特定症状和AD抗性相关的遗传因素的适当模型。(C) 2008 Elsevier Ltd版权所有。
Etiopathogenesis of depression and the cause of insensitivity to treatment remain poorly understood, although genetic makeup has been established as a contributing factor. The isogenicity of inbred mouse strains provides a useful toot for investigating the link between genes and behavior or drug response. Hence, our aim was to identify inbred mouse strains (among A/J, BALB/c, C3H, C57BL/6, CBA, DBA and FVB) sensitive to a 9-week period of unpredictable chronic mild stress (UCMS) and, from the fifth week onward, to the reversal effect of an antidepressant (AD) (imipramine, 20 mg/kg/day i.p.) on various depression-related changes: physical, behavioral and neuroendocrine states. UCMS induced a significant deterioration of the coat state (in all the strains), blunted emotional reactivity in the novelty-suppressed feeding (NSF) test (A/J, BALB/c, C57BL/6), and changes in the level of fecal corticosterone metabolites (BALB/c, C57BL/6, DBA, FVB). Imipramine treatment reversed the UCMS-induced alterations of the coat state (BALB/c, DBA), in the NSF test (A/J, BALB/c, C57BL/6) and in fecal corticosterone metabolites (BALB/c, C57BL/6). C3H, CBA and FVB mice were irresponsive to imipramine treatment. It is noteworthy that UCMS-induced physical or behavioral changes occurred without hypothalamo-pituitary-adrenal (HPA) axis alterations in some strains (A/J, C3H, CBA), although the AD-induced reversal of these changes in BALB/c and C57BL/6 was associated with HPA axis normalization. Finally, UCMS is shown to discriminate various alterations and to replicate in a strain-dependent manner diverse profiles reminiscent of human disease subtypes. UCMS may thus enable the selection of strains suitable for investigating specific depression-related features and could be an appropriate model for identifying genetic factors associated with increased vulnerability, specific symptoms of affective disorders, and AD resistance. (C) 2008 Elsevier Ltd. All rights reserved.