Environmental enrichment influences novelty reactivity, novelty preference, and anxiety via distinct genetic mechanisms in C57BL/6J and DBA/2J mice.

Environmental enrichment influences novelty reactivity, novelty preference, and anxiety via distinct genetic mechanisms in C57BL/6J and DBA/2J mice.
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环境富集通过不同的遗传机制影响C57BL/6J和DBA/2J小鼠的新奇反应性、新奇偏好和焦虑。

DOI:
10.1038/s41598-021-83574-6
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发表时间:
2021-02-16
期刊:
影响因子:
4.6
通讯作者:
Mittleman G
Mittleman G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dickson PE;Mittleman G

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压力等环境因素促使基因脆弱的个体产生药物成瘾;这种脆弱性背后的基因是未知的。揭示这些基因的一个策略是研究环境操纵对预测药物使用和成瘾行为的高通量表型的影响。在目前的研究中,我们通过评估环境富集和隔离住房对三种高通量表型的相对影响来评估这种方法的可行性,这些表型已知可预测静脉注射药物自我给药的不同方面的变化。在行为测试之前,将雄性和雌性C57BL/6J和DBA/2J小鼠(BXD创始人)从断奶开始进行富集或隔离饲养10周。富集显著降低新奇反应性;这种效应在C57BL/6J小鼠中明显强于DBA/2J小鼠。富集显著降低新奇偏好;这种效应明显依赖于新的环境特征,并且在DBA/2J小鼠中相对于C57BL/6J小鼠更为强大。富集显著增加焦虑;这种效应不依赖于菌株。综上所述,这些数据表明:(1)环境富集通过不同的遗传机制影响小鼠的新奇反应性、新奇偏好和焦虑;(2)BXD面板可以用来发现这一现象背后的遗传和表观遗传机制。
Environmental factors such as stress drive the development of drug addiction in genetically vulnerable individuals; the genes underlying this vulnerability are unknown. One strategy for uncovering these genes is to study the impact of environmental manipulation on high-throughput phenotypes that predict drug use and addiction-like behaviors. In the present study, we assessed the viability of this approach by evaluating the relative effects of environmental enrichment and isolation housing on three high-throughput phenotypes known to predict variation on distinct aspects of intravenous drug self-administration. Prior to behavioral testing, male and female C57BL/6J and DBA/2J mice (BXD founders) were housed in enrichment or isolation for ten weeks beginning at weaning. Enrichment significantly reduced novelty reactivity; this effect was significantly more robust in C57BL/6J mice relative to DBA/2J mice. Enrichment significantly reduced novelty preference; this effect was significantly dependent on novel environment characteristics and was significantly more robust in DBA/2J mice relative to C57BL/6J mice. Enrichment significantly increased anxiety; this effect was not strain-dependent. Collectively, these data indicate that (1) environmental enrichment influences novelty reactivity, novelty preference, and anxiety via distinct genetic mechanisms in mice, and (2) the BXD panel can be used to discover the genetic and epigenetic mechanisms underlying this phenomenon.
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