Zhang Fan, Yuan Sanna, Shao Feng, Wang Weiwen
Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of SciencesBeijing, China; The University of Chinese Academy of SciencesBeijing, China.
Department of Psychology and Beijing Key Laboratory of Behavior and Mental Health, Peking University Beijing, China.
Front Behav Neurosci. 2016 Jul 20;10:149. doi: 10.3389/fnbeh.2016.00149. eCollection 2016.
Negative social experiences during adolescence increase the risk of psychiatric disorders in adulthood. Using "resident-intruder" stress, the present study aimed to investigate the effects of adolescent social defeat on emotional and cognitive symptoms associated with psychiatric disorders during adulthood and the effects of the developmental stage and social condition on this process. In Experiment 1, animals were exposed to social defeat or manipulation for 10 days during early adolescence (EA, postnatal days [PND] 28-37), late adolescence (LA, PND 38-47), and adulthood (ADULT, PND 70-79) and then singly housed until the behavioral tests. Behaviors, including social avoidance of the defeat context and cortically mediated cognitive flexibility in an attentional set-shifting task (AST), were assessed during the week following stress or after 6 weeks during adulthood. We determined that social defeat induced significant and continuous social avoidance across age groups at both time points. The mice that experienced social defeat during adulthood exhibited short-term impairments in reversal learning (RL) on the AST that dissipated after 6 weeks. In contrast, social defeat during EA but not LA induced a delayed deficit in extra-dimensional set-shifting (EDS) in adulthood but not during adolescence. In Experiment 2, we further examined the effects of social condition (isolation or social housing after stress) on the alterations induced by social defeat during EA in adult mice. The adult mice that had experienced stress during EA exhibited social avoidance similar to the avoidance identified in Experiment 1 regardless of the isolation or social housing after the stress. However, social housing after the stress ameliorated the cognitive flexibility deficits induced by early adolescent social defeat in the adult mice, and the social condition had no effect on cognitive function. These findings suggest that the effects of social defeat on emotion and cognitive function are differentially affected by the developmental stage and social condition. EA may comprise a particularly sensitive developmental period in which social defeat may produce a delayed impairment in cognitive flexibility during adulthood, and the social condition following stress appears to play an important intermediary role in the development of these cognitive deficits.
青春期的负面社会经历会增加成年后患精神疾病的风险。本研究利用“居住者-入侵者”应激模型，旨在探究青春期社会挫败对成年期与精神疾病相关的情绪和认知症状的影响，以及发育阶段和社会环境对这一过程的影响。在实验1中，将动物在青春期早期（EA，出生后第28 - 37天）、青春期晚期（LA，出生后第38 - 47天）和成年期（ADULT，出生后第70 - 79天）暴露于社会挫败或假处理10天，然后单独饲养直至进行行为测试。在应激后的一周内或成年期6周后，评估包括对挫败情境的社会回避以及在注意力转换任务（AST）中皮质介导的认知灵活性等行为。我们确定，在两个时间点，社会挫败在各年龄组中均诱发了显著且持续的社会回避。成年期经历社会挫败的小鼠在AST的逆向学习（RL）中表现出短期损伤，6周后消失。相比之下，青春期早期而非晚期的社会挫败在成年期而非青春期诱发了维度外转换（EDS）的延迟缺陷。在实验2中，我们进一步研究了社会环境（应激后隔离或群居）对成年小鼠青春期早期社会挫败所诱发改变的影响。青春期早期经历过应激的成年小鼠，无论应激后是隔离还是群居，均表现出与实验1中所确定的回避相似的社会回避。然而，应激后的群居改善了成年小鼠青春期早期社会挫败所诱发的认知灵活性缺陷, 且社会环境对认知功能没有影响。这些发现表明，社会挫败对情绪和认知功能的影响受到发育阶段和社会环境的不同影响。青春期早期可能是一个特别敏感的发育时期，在此期间社会挫败可能会在成年期产生认知灵活性的延迟损伤，应激后的社会环境似乎在这些认知缺陷的发展中起着重要的中介作用。
