Adolescent social defeat decreases spatial working memory performance in adulthood.
Adolescent social defeat decreases spatial working memory performance in adulthood.
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DOI：
10.1186/1744-9081-9-39
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发表时间：
2013-10-17
期刊：
影响因子：
--
通讯作者：
Watt MJ
中科院分区：
文献类型：
--
作者：
Novick AM;Miiller LC;Forster GL;Watt MJ
青少年社会压力与成年后精神疾病的发病率增加有关，其特点是认知焦点和灵活性缺陷。这种脆弱性的增强可能是由于心理社会压力引起的中皮层多巴胺系统的发育破坏，该系统在促进空间工作记忆等复杂的认知过程中发挥着重要作用。作为社交压力模型，暴露于反复社交失败的青春期大鼠成年后内侧前额叶皮层会出现多巴胺能功能减退。为了评估青少年社交压力与后来认知功能缺陷之间的直接联系，本研究测试了青少年社交失败对空间工作记忆表现的两项独立测试的影响。暴露于青少年社交失败的成年大鼠及其对照组接受了延迟双赢任务或延迟交替 T 迷宫任务的训练，然后接受不同延迟期的挑战。为了评估记忆任务中使用食物奖励的动机的潜在差异，在先前击败的大鼠和对照组的单独队列中测试了对甜炼乳的消耗和条件位置偏好。与对照组相比，在青春期失败的成年大鼠在空间工作记忆表现上表现出延迟依赖性缺陷，在 T 迷宫和 win-shift 任务中分别在 90 秒和 5 分钟延迟期间犯下更多错误。观察到的记忆缺陷可能与奖励动机的差异无关，因为青少年社交失败组和对照组对两项任务中使用的可口食物的条件性位置偏好相似。结果表明，青春期期间严重的社会压力可能会导致认知功能方面的长期缺陷。鉴于空间工作记忆对前额叶多巴胺的依赖性，通过药物逆转青少年社会压力引起的多巴胺能缺陷有可能治疗此类认知缺陷。
Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance. Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls. Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control. The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits.
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