Chronic social defeat stress gives rise to social avoidance through fear learning

IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Behavioural Brain Research Pub Date : 2024-09-04 DOI:10.1016/j.bbr.2024.115245
Jinah Lee , Antonio Aubry , Sadiyah Hanif , Itamar S. Grunfeld , Ekaterina Likhtik , Nesha S. Burghardt
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Abstract

Chronic social defeat stress (CSDS), a widely used rodent model of stress, reliably leads to decreased social interaction in stress susceptible animals. Here, we investigate a role for fear learning in this response using male 129 Sv/Ev mice, a strain that is more vulnerable to CSDS than the commonly used C57BL/6 strain. We first demonstrate that defeated 129 Sv/Ev mice avoid a CD-1 mouse, but not a conspecific, indicating that motivation to socialize is intact in this strain. CD-1 avoidance is characterized by approach behavior that results in running in the opposite direction, activity that is consistent with a threat response. We next test whether CD-1 avoidance is subject to the same behavioral changes found in traditional models of Pavlovian fear conditioning. We find that associative learning occurs across 10 days CSDS, with defeated mice learning to associate the color of the CD-1 coat with threat. This leads to the gradual acquisition of avoidance behavior, a conditioned response that can be extinguished with 7 days of repeated social interaction testing (5 tests/day). Pairing a CD-1 with a tone leads to second-order conditioning, resulting in avoidance of an enclosure without a social target. Finally, we show that social interaction with a conspecific is a highly variable response in defeated mice that may reflect individual differences in generalization of fear to other social targets. Our data indicate that fear conditioning to a social target is a key component of CSDS, implicating the involvement of fear circuits in social avoidance.

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慢性社交失败压力通过恐惧学习产生社交回避。
慢性社会挫败应激(CSDS)是一种广泛使用的啮齿动物应激模型,它能可靠地导致应激易感动物的社会互动减少。在这里,我们使用雄性 129Sv/Ev 小鼠研究了恐惧学习在这种反应中的作用,这种小鼠比常用的 C57BL/6 品系更容易受到 CSDS 的影响。我们首先证明,被打败的 129Sv/Ev 小鼠会躲避 CD-1 小鼠,但不会躲避同种小鼠,这表明该品系小鼠的社交动机是完整的。CD-1回避的特点是接近行为导致向相反方向奔跑,这种活动与威胁反应一致。我们接下来要测试的是,CD-1 的回避行为是否与传统巴甫洛夫恐惧条件反射模型中的行为变化相同。我们发现,联想学习发生在 10 天的 CSDS 期间,被打败的小鼠学会了将 CD-1 外衣的颜色与威胁联系起来。这导致小鼠逐渐获得回避行为,这种条件反应可以通过 7 天的重复社会互动测试(每天 5 次测试)来消除。将 CD-1 与音调配对会产生二阶条件反射,从而导致回避没有社交目标的围栏。最后,我们表明,与同种小鼠的社会互动是败育小鼠的一个高度可变的反应,这可能反映了个体在将恐惧泛化到其他社会目标方面的差异。我们的数据表明,对社交目标的恐惧条件反射是 CSDS 的关键组成部分,这意味着恐惧回路参与了社交回避。
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来源期刊
Behavioural Brain Research
Behavioural Brain Research 医学-行为科学
CiteScore
5.60
自引率
0.00%
发文量
383
审稿时长
61 days
期刊介绍: Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.
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