Differential effects of acute and chronic social defeat stress on hypothalamic-pituitary-adrenal axis function and hippocampal serotonin release in mice
Differential effects of acute and chronic social defeat stress on hypothalamic-pituitary-adrenal axis function and hippocampal serotonin release in mice
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DOI：
10.1111/j.1365-2826.2006.01422.x
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发表时间：
2006-05-01
影响因子：
3.2
通讯作者：
Blackburn-Munro, RE
中科院分区：
文献类型：
--
作者：
Keeney, A;Jessop, DS;Blackburn-Munro, RE
下丘脑-垂体-肾上腺（HPA）应激轴的过度活跃和5-羟色胺（5-HT）神经传递的紊乱与抑郁症的发病机制有关。雄性NMRI小鼠的反复社交失败已被证明会诱导核心体温和皮质酮的增加，这表明从属动物处于慢性应激状态。本研究进一步表征了HPA轴对社交失败应激的反应，并研究了应激过程中海马细胞外5-HT的释放。暴露于一个急性社会失败elections增加血浆促肾上腺皮质激素和皮质酮水平，分别在15和30分钟达到峰值，并增强促肾上腺皮质激素释放因子（CRF）的mRNA，但不精氨酸加压素（AVP）mRNA内侧小细胞分裂下丘脑室旁核。观察到海马皮质酮和5-HT水平的伴随增加。相比之下，虽然慢性社交失败与皮质酮水平大幅升高有关，但主要驱动力似乎是通过小细胞AVP而不是CRF。此外，下属动物允许恢复9天后，慢性社会失败显示增加不动性强迫游泳抑郁症模型，表明动物以前暴露于同型失败压力敏感的行为影响的一种新的压力。这些结果表明，社会失败诱导HPA轴的长期激活和5-HT神经传递的改变，可能与临床抑郁症中观察到的一些病理异常有关。
Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) stress axis and disturbances in serotonin (5-HT) neurotransmission have been implicated in the pathogenesis of depressive disorder. Repeated social defeat of male NMRI mice has been shown to induce increases in core body temperature and corticosterone, indicative of a state of chronic stress in subordinate animals. The present study further characterised the HPA axis response to social defeat stress, and also examined hippocampal extracellular 5-HT release during the stress. Exposure to an acute social defeat elicits increases in plasma adrenocorticotrophic hormone and corticosterone levels, peaking at 15 and 30 min, respectively, and enhances corticotrophin-releasing factor (CRF) mRNA, but not arginine vasopressin (AVP) mRNA within the medial parvocellular division of the hypothalamic paraventricular nucleus. A concomitant increase in hippocampal corticosterone and 5-HT levels is observed. By contrast, although chronic social defeat is associated with greatly elevated corticosterone levels, the predominant drive appears to be via parvocellular AVP rather than CRF. Furthermore, subordinate animals allowed to recover for 9 days after chronic social defeat display an increase in immobility in the forced swimming model of depression, indicating that animals previously exposed to the homotypic defeat stress are sensitised to the behavioural effects of a novel stressor. These results demonstrate that social defeat induces prolonged activation of the HPA axis and alterations in 5-HT neurotransmission that could be of relevance to some of the pathological abnormalities observed in clinical depression.