Phenotypic responses to social defeat are associated with differences in cued and contextual fear discrimination
Phenotypic responses to social defeat are associated with differences in cued and contextual fear discrimination
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DOI：
10.1016/j.beproc.2015.06.009
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发表时间：
2015-09-01
影响因子：
1.3
通讯作者：
Jasnow, Aaron M.
中科院分区：
文献类型：
--
作者：
Dulka, Brooke N.;Lynch, Joseph F., III;Jasnow, Aaron M.
个体之间的冲突是包括人类在内的各种物种经历的最常见的压力源之一。在小鼠的社交失败模型中，产生两种表型行为反应，其特征是长期的社交回避(易感性)或持续的社交互动(抵触)。这种抗性表型被认为是人类对慢性应激诱导的抑郁的一种恢复力模型。此前，我们已经发现，对社会失败压力具有抵抗力的小鼠在灭绝学习和保持方面表现出显著的损害，这表明在经历社会失败后持续的社会互动可能与适应不良的恐惧反应有关。在这里，我们研究了个体对社会失败的反应差异如何与线索和背景恐惧歧视的差异有关。失败后，与对照和敏感小鼠相比，耐受小鼠对中性提示刺激(CS-)表现出更多的恐惧，但仍然能够显著区分CS+和CS-。同样，在所有测试的保持间隔(1、5、14天)中，两种表型通常都能够区分训练背景和中性背景。然而，在评估辨别率时，易感小鼠表现出比抵抗和未被击败的对照组小鼠更好的辨别能力。因此，在大多数动物开始对背景线索表现出泛化的时候，敏感的小鼠保持着区分恐惧和中性背景的能力。这些数据表明，在环境中观察到的差异以及敏感和抗性小鼠之间的线索歧视可能与它们在应对社会失败时的应对策略不同有关。特别是，传统上对社会失败的抵抗力或恢复力可能与改变的抑制性学习有关。了解个体在应对压力时产生的差异，包括社会对抗，对于理解与压力相关的疾病的发展和治疗，如创伤后应激障碍，是很重要的。(C)2015爱思唯尔B.V.保留所有权利。
Conflict among individuals is one of the most common forms of stressors experienced across a variety of species, including humans. Social defeat models in mice produce two phenotypic behavioral responses characterized by prolonged social avoidance (susceptibility) or continued social interaction (resistance). The resistant phenotype has been proposed as a model of resilience to chronic stress-induced depression in humans. Previously, we have found that mice that are resistant to social defeat stress display significant impairments in extinction learning and retention, suggesting that continued social interaction following the experience of social defeat may be associated with maladaptive fear responses. Here, we examined how individual differences in response to social defeat may be related to differences in cued and context fear discrimination. Following defeat, resistant mice showed increased fear to a neutral cued stimulus (CS-) compared to control and susceptible mice, but were still able to significantly discriminate between the CS+ and CS-. Likewise, both phenotypes were generally able to discriminate between the training context and neutral context at all retention intervals tested (1, 5, 14 days). However, susceptible mice displayed significantly better discrimination compared to resistant and non-defeated control mice when assessing the discrimination ratio. Thus, at a time when most animals begin exhibiting generalization to contextual cues, susceptible mice retain the ability to discriminate between fearful and neutral contexts. These data suggest that the differences observed in context and cued discrimination between susceptible and resistant mice may be related to differences in their coping strategies in response to social defeat. In particular, resistance or resilience to social defeat as traditionally characterized may be associated with altered inhibitory learning. Understanding why individual differences arise in response to stress, including social confrontation is important in understanding the development and treatment of stress related pathologies such as PTSD. (C) 2015 Elsevier B.V. All rights reserved.