Strain and sex dependent effects of isolation housing relative to environmental enrichment on operant sensation seeking in mice.
Strain and sex dependent effects of isolation housing relative to environmental enrichment on operant sensation seeking in mice.
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DOI：
10.1038/s41598-021-97252-0
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发表时间：
2021-09-08
影响因子：
4.6
通讯作者：
Mittleman G
中科院分区：
文献类型：
--
作者：
Dickson PE;Mittleman G
感觉寻求是一种多维表型，可预测人类药物成瘾和啮齿动物成瘾样药物寻求的发展。一些证据表明，慢性压力通过常见的遗传机制增加了感觉寻求和成瘾性药物寻求。这些机制的发现和表征将揭示慢性压力如何与基因组相互作用以影响感觉寻求，以及滥用药物如何劫持这些基本的奖励机制以驱动成瘾。为此，我们测试的假设，慢性隔离住房压力（相对于丰富的环境）影响操作性感觉寻求应变，性别，或它们的相互作用的函数。为了确定BXD重组近交系组是否可用于鉴定任何鉴定的基因与环境相互作用的遗传和表观遗传机制，我们使用了来自两个BXD创始品系的小鼠。经过10周的差异住房，我们评估了操作性感觉寻求使用几种强化时间表。这项研究的主要发现是，DBA/2 J而不是C57 BL/6 J小鼠在灭绝期间，当感觉奖励不再可用时，明显容易受到隔离诱导的感觉寻求增加（相对于环境丰富）的影响;这种影响在雌性小鼠中明显更强。这些数据揭示了一个以前未知的隔离诱导的影响，灭绝的操作性感觉寻求是性别依赖性的，成瘾相关的，可以解剖使用BXD重组近交面板。
Sensation seeking is a multidimensional phenotype that predicts the development of drug addiction in humans and addiction-like drug seeking in rodents. Several lines of evidence suggest that chronic stress increases sensation seeking and addiction-like drug seeking through common genetic mechanisms. Discovery and characterization of these mechanisms would reveal how chronic stress interacts with the genome to influence sensation seeking and how drugs of abuse hijack these fundamental reward mechanisms to drive addiction. To this end, we tested the hypothesis that chronic isolation housing stress (relative to environmental enrichment) influences operant sensation seeking as a function of strain, sex, or their interaction. To determine if the BXD recombinant inbred panel could be used to identify genetic and epigenetic mechanisms underlying any identified gene-by-environment interactions, we used mice from the two BXD founder strains. Following 10 weeks of differential housing, we assessed operant sensation seeking using several reinforcement schedules. The primary finding from this study was that DBA/2J but not C57BL/6J mice were significantly vulnerable to an isolation-induced increase (relative to environmental enrichment) in sensation seeking during extinction when the sensory reward was no longer available; this effect was significantly more robust in females. These data reveal a previously unknown isolation-induced effect on extinction of operant sensation seeking that is sex-dependent, addiction-relevant, and that can be dissected using the BXD recombinant inbred panel.
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