Antidepressants and the resilience to early-life stress in inbred mouse strains
Antidepressants and the resilience to early-life stress in inbred mouse strains
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DOI：
10.1097/fpc.0b013e32834b3f35
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发表时间：
2011-12-01
影响因子：
2.6
通讯作者：
Schalkwyk, Leonard C.
中科院分区：
文献类型：
--
作者：
Binder, Elke;Malki, Karim;Schalkwyk, Leonard C.
为患有严重抑郁障碍的患者选择有效的治疗方法是精神病学家长期面临的问题。目的小鼠近交系小鼠在抑郁相关行为测试中的基线表现不同，最初被确认为抗抑郁反应的测试。方法我们的研究设计包括四个近交系小鼠(129S1/SvlmJ，C57LB/6J，DBA/2J和FVB/NJ)，其中两个接受环境操作(母体分离和不可预测的慢性轻度应激)，两个接受抗抑郁药物治疗的代表(艾司匹兰和去甲胰腺素与载体)。接受抗抑郁药物治疗的小鼠被进一步分为急性(1天)和亚慢性(14天)两组，总共有144个实验组，每个实验组至少有7只动物。用Porsolt强迫游泳试验(FST)和孔板试验对所有动物进行测试。结果尽管有24小时的母体分离(MS)或14天不可预测的慢性轻度应激方案，大多数动物似乎对诱导的应激具有弹性。一个令人信服的发现是，多发性硬化症的长期、特定的菌株效应导致Porsolt FST中抑郁样行为的增加，以及在129S1/SvImJ小鼠的孔板测试中看到的与焦虑相关的行为增加。去甲替林可有效逆转129S1/SvlmJ雄性小鼠FST中MS的作用。结论出生后第9天母鼠与母鼠分离24小时，足以导致成年129S1/SvImJ小鼠出现抑郁样表型，而在C57LB/6 J、DBA/2 J和FVB/NJ小鼠中则不能。药物遗传学和基因组学21：779-789(C)2011年沃尔特斯·克鲁沃健康垂直条Lippincott Williams&Wilkins。
Rationale Selecting an effective treatment for patients with major depressive disorder is a perpetual problem for psychiatrists. It is of particular interest to explore the interaction between genetic predisposition and environmental factors.Objectives Mouse inbred strains vary in baseline performance in depression-related behaviour tests, which were originally validated as tests of antidepressant response. Therefore, we investigated interactions between environmental stress, genotype, and drug response in a multifactorial behaviour study.Method Our study design included four inbred mouse strains (129S1/SvlmJ, C57LB/6J, DBA/2J and FVB/NJ) of both sexes, two subjected to environmental manipulations (maternal separation and unpredictable chronic mild stress) and two representative of treatment with antidepressants (escitalopram and nortryptiline vs. vehicle). The mice treated with antidepressants were further divided into those administered acute (1 day) and subchronic (14 days) regimes, giving 144 experimental groups in all, each with at least seven animals. All animals were tested using the Porsolt forced-swim test (FST) and the hole-board test.Results Despite a 24-h maternal separation (MS) or a 14-day unpredictable chronic mild stress protocol, most animals seemed to be resilient to the stress induced. One compelling finding is the long-lasting, strain-specific effect of MS resulting in an increased depression-like behaviour in the Porsolt FST and elevated anxiety-related behaviour in the hole-board test seen in 129S1/SvImJ mice. Nortriptyline was effective in reversing the effect of MS in the FST in 129S1/SvlmJ male mice.Conclusion A single 24-h maternal separation of pups from their mother on postnatal day 9 is a sufficient insult to result in a depression-like phenotype in adult 129S1/SvImJ mice but not in C57LB/6 J, DBA/2 J, and FVB/NJ mice. Pharmacogenetics and Genomics 21:779-789 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.