Luo Xiao-Min, Yuan San-Na, Guan Xi-Ting, Xie Xi, Shao Feng, Wang Wei-Wen
The University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
Department of Psychology, Peking University, Beijing 100871, China.
Physiol Behav. 2014 Aug;135:7-16. doi: 10.1016/j.physbeh.2014.05.035. Epub 2014 Jun 4.
Epidemiological evidence suggests that childhood and adolescent maltreatment is a major risk factor for mood disorders in adulthood. However, the mechanisms underlying the manifestation of mental disorders during adulthood are not well understood. Using a recently developed rat model for assessing chronic variable stress (CVS) during early adolescence (juvenility), we investigated the long-term effects of juvenile CVS on emotional and cognitive function and on monoaminergic activities in the limbic areas. During juvenility (postnatal days 27-33), rats in the stress group were exposed to variable stressors every other day for a week. Four weeks later, anhedonia was tested in the sucrose test, anxiety-like behaviors were assessed in the elevated plus-maze (EPM) and open field (OF) tests, and cortically mediated cognitive function was evaluated during an attentional set-shifting task (AST). After the behavioral tests, the rats were decapitated to determine limbic monoamine and metabolite levels. Adult rats stressed during juvenility exhibited higher anxiety-like behaviors, as evidenced by reduced locomotion and rearing behavior in the OF and fewer entries into the open arms in the EPM. There were no differences between the stressed rats and the controls in depressive-like anhedonia during the sucrose preference test or in cognitive function during the AST test in adulthood. In addition, the previously stressed rats exhibited increased dopamine (DA) and decreased 5-HIAA in the medial prefrontal cortex (mPFC) and decreased noradrenaline in the amygdala compared with controls. Furthermore, DA levels in the mPFC were correlated with adult anxious behaviors in the OF. These results suggest that juvenile stress induces long-term changes in the expression of anxiety-like behaviors and limbic monoaminergic activity in adult rats.
流行病学证据表明，儿童期和青少年期受虐待是成年后患情绪障碍的主要风险因素。然而，成年期精神障碍表现背后的机制尚未完全明确。我们使用最近开发的一种用于评估青春期早期（幼年）慢性可变应激（CVS）的大鼠模型，研究了幼年CVS对情绪和认知功能以及边缘区域单胺能活动的长期影响。在幼年时期（出生后第27 - 33天），应激组的大鼠每隔一天接受一次可变应激源刺激，持续一周。四周后，在蔗糖试验中测试快感缺失，在高架十字迷宫（EPM）和旷场（OF）试验中评估焦虑样行为，并在注意力转换任务（AST）期间评估皮质介导的认知功能。行为测试后，将大鼠断头以测定边缘单胺和代谢物水平。幼年时期受应激的成年大鼠表现出更高的焦虑样行为，表现为在旷场试验中运动和站立行为减少，以及在高架十字迷宫试验中进入开放臂的次数减少。在成年期的蔗糖偏好试验中，应激大鼠和对照组在类似抑郁的快感缺失方面没有差异，在AST试验中的认知功能也没有差异。此外，与对照组相比，先前受应激的大鼠内侧前额叶皮质（mPFC）中的多巴胺（DA）增加，5 - 羟吲哚乙酸（5 - HIAA）减少，杏仁核中的去甲肾上腺素减少。此外，内侧前额叶皮质中的多巴胺水平与成年大鼠在旷场试验中的焦虑行为相关。这些结果表明，幼年应激会诱导成年大鼠焦虑样行为表达和边缘单胺能活动的长期变化。
