Background

Mouse models of social behavior fail to account for volitional aspects of social interaction, and current neurobiological investigation of social behavior is performed almost exclusively using C57BL/6J mice, the background strain of most transgenic mice. Here, we introduce a mouse model of operant social self-administration and choice, using a custom-made apparatus.

Methods

First, we trained adolescent and adult female C57BL/6J and CD1 mice to self-administer palatable food pellets and then to lever press under increasing fixed-ratio response requirements for access to an age-matched female social partner. Next, we tested their motivation to seek social interaction using a progressive ratio reinforcement schedule, relapse to social seeking after social isolation, and choice between palatable food versus social interaction. We also tested social conditioned place preference in adult female CD1 and C57BL/6J mice.

Results

Adolescent and adult female mice of both strains showed similar rates of food self-administration. In contrast, CD1 mice demonstrated significantly stronger social self-administration than C57BL/6J mice under both reinforcement schedules. CD1 but not C57BL/6J mice demonstrated robust social seeking after social isolation. In the choice task, CD1 mice preferred social interaction, whereas C57BL/6J mice preferred food. CD1 but not C57BL/6J mice demonstrated robust social conditioned place preference. The strain differences were age independent.

Conclusions

Our data show that CD1 mice are a better strain for studying female social reward learning. Our mouse operant social model provides a tool for research on neurobiological substrates of female social reward and disruption of social reward in psychiatric disorders using mouse-specific genetic tools.

中文翻译：

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透过窗户挥手：雌性小鼠自愿社会互动模型

背景

社交行为的小鼠模型无法解释社交互动的意志方面，目前对社交行为的神经生物学研究几乎完全使用 C57BL/6J 小鼠进行，C57BL/6J 小鼠是大多数转基因小鼠的背景品系。在这里，我们使用定制设备介绍了操作性社会自我管理和选择的鼠标模型。

方法

首先，我们训练青春期和成年雌性 C57BL/6J 和 CD1 小鼠自我喂食可口的食物颗粒，然后在越来越多的固定比率反应要求下利用压力来接触年龄匹配的女性社会伙伴。接下来，我们测试了他们使用渐进比率强化计划寻求社交互动的动机、在社交隔离后回归社交以及在可口食物与社交互动之间做出选择。我们还测试了成年雌性 CD1 和 C57BL/6J 小鼠的社会条件性位置偏好。

结果

两种品系的青春期和成年雌性小鼠表现出相似的食物自我管理率。相比之下，在两种强化方案下，CD1 小鼠的社会自我管理能力明显强于 C57BL/6J 小鼠。CD1 而不是 C57BL/6J 小鼠在社会隔离后表现出强烈的社会寻求。在选择任务中，CD1 小鼠更喜欢社交互动，而 C57BL/6J 小鼠更喜欢食物。CD1 而不是 C57BL/6J 小鼠表现出强烈的社会条件性位置偏好。应变差异与年龄无关。

结论

我们的数据表明，CD1 小鼠是研究女性社会奖励学习的更好品系。我们的小鼠操作性社会模型提供了一种工具，用于使用小鼠特异性遗传工具研究女性社会奖励的神经生物学底物和精神疾病中社会奖励的破坏。