Social vs. environmental stress models of depression from a behavioural and neurochemical approach
Social vs. environmental stress models of depression from a behavioural and neurochemical approach
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DOI：
10.1016/j.euroneuro.2012.05.010
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发表时间：
2013-07
影响因子：
5.6
通讯作者：
E. Venzala;A. L. Garcia-Garcia-A.-L.-Garcia-Garcia-79423717;N. Elizalde;R. Tordera
中科院分区：
文献类型：
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作者：
E. Venzala;A. L. Garcia-Garcia-A.-L.-Garcia-Garcia-79423717;N. Elizalde;R. Tordera
重度抑郁症是一种精神障碍，通常在暴露于慢性压力或压力性生活事件之后发生。最近，与慢性轻度应激（CMS）等环境模型相比，基于社会冲突的动物模型（例如慢性社交失败应激（CSDS））被认为与应激诱发的人类精神病理学更相关。然而，虽然 CMS 再现了特定的核心抑郁症状，例如快感缺乏和无助，但 CSDS 研究依赖于对压力引起的社交回避的分析，解决不同的神经精神疾病。在这里，我们从行为和神经化学方法比较研究这两种模型及其与人类抑郁症的可能相关性。小鼠 (C57BL/6) 暴露于 CMS 或 CSDS 六周零十天。定期评估快感缺失。压力程序后第四周进行的一系列测试包括运动活动、记忆力、焦虑、社交互动和无助感。随后，我们检查了前额皮质、海马和脑干中的谷氨酸、GABA、5-HT 和多巴胺水平。 CMS 诱发了明显的抑郁样特征，包括快感缺乏、无助和记忆障碍。 CSDS 会引起快感缺乏、多动、焦虑和社交回避，这些症状也是焦虑和创伤后应激障碍的常见症状。虽然两种模型都破坏了前额皮质的兴奋性抑制平衡，但 CMS 显着改变了脑干的这种平衡。此外，CSDS 降低了前额皮质和脑干中的多巴胺。我们认为，虽然抑郁样行为可能与皮质和脑干区域氨基酸神经传递的改变有关，但 CSDS 诱导的焦虑行为可能与奖励过程中涉及的多巴胺能通路的特定改变有关。
Major depression is a mental disorder often preceded by exposure to chronic stress or stressful life events. Recently, animal models based on social conflict such as chronic social defeat stress (CSDS) are proposed to be more relevant to stress-induced human psychopathology compared to environmental models like the chronic mild stress (CMS). However, while CMS reproduces specifically core depressive symptoms such as anhedonia and helplessness, CSDS studies rely on the analysis of stress-induced social avoidance, addressing different neuropsychiatric disorders. Here, we study comparatively the two models from a behavioural and neurochemical approach and their possible relevance to human depression. Mice (C57BL/6) were exposed to CMS or CSDS for six weeks and ten days. Anhedonia was periodically evaluated. A battery of test applied during the fourth week after the stress procedure included motor activity, memory, anxiety, social interaction and helplessness. Subsequently, we examined glutamate, GABA, 5-HT and dopamine levels in the prefrontal cortex, hippocampus and brainstem. CMS induced a clear depressive-like profile including anhedonia, helplessness and memory impairment. CSDS induced anhedonia, hyperactivity, anxiety and social avoidance, signs also common to anxiety and posttraumatic stress disorders. While both models disrupted the excitatory inhibitory balance in the prefrontal cortex, CMS altered importantly this balance in the brainstem. Moreover, CSDS decreased dopamine in the prefrontal cortex and brainstem. We suggests that while depressive-like behaviours might be associated to altered aminoacid neurotransmission in cortical and brain stem areas, CSDS induced anxiety behaviours might be linked to specific alteration of dopaminergic pathways involved in rewarding processes.