Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains
Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains
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DOI：
10.1016/j.bbr.2005.01.005
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发表时间：
2005-06-03
影响因子：
2.7
通讯作者：
Papadopoulou-Daifoti, Z
中科院分区：
文献类型：
--
作者：
Bekris, S;Antoniou, K;Papadopoulou-Daifoti, Z
据报道，慢性轻度应激（CMS）会导致大鼠出现快感缺失状态，类似于人类内源性抑郁症的一些症状。在本研究中，在 Wistar 和 Sprague-Dawley 大鼠接受丙咪嗪治疗后，检查了 CMS 诱导的行为反应以及前额皮质、纹状体、下丘脑和海马多巴胺能和血清素能功能的神经化学变化。 CMS 程序总共持续了 7 周。每周一次，进行 1 小时对 1% 蔗糖溶液的偏好测试。实验第 3 周后开始用丙咪嗪（10 mg/kg 腹腔注射，每天一次）治疗。CMS 诱导两种大鼠品系的绝对和相对蔗糖摄入量以及蔗糖偏好显着降低，但它们的时间模式不同，特别是在第 0-3 周期间。 IMI 逆转了这些影响。 CMS 后，两种大鼠品系的前额皮质中均观察到多巴胺能增加和血清素能活性降低。在 CMS 后，两种大鼠品系中也观察到纹状体多巴胺能活性降低和海马血清素能活性增加。在 Wistar 大鼠中，下丘脑的多巴胺能和血清素能活性增强，而在 Sprague-Dawley 大鼠中没有观察到这种应激引起的变化。值得注意的是，在应激 Wistar 大鼠中观察到的蔗糖消耗明显减少可能与多巴胺能下丘脑活动的相应增加直接相关。丙咪嗪的长期治疗使 CMS 引起的所有神经化学变化正常化。我们的结果表明，特定的、区域差异的血清素-多巴胺相互作用与观察到的压力诱发的快感缺失直接相关。 (c) 2005 年 Elsevier B.V. 出版
Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in rats that resembles some of the symptoms of endogenous depression in humans. In the present study, CMS-induced behavioural responses along with neurochemical alterations in dopaminergic and serotonergic function in prefrontal cortex, striatum, hypothalamus and hippocampus were examined following treatment with imipramine in Wistar and Sprague-Dawley rats. The CMS procedure lasted 7 weeks in total. Once per week, a 1-h preference test for 1% sucrose solution was conducted. Treatment with imipramine (10 mg/kg i.p., once daily) commenced after experimental week 3. CMS induced significant reductions in absolute and relative sucrose intake and sucrose preference in both rat strains but their temporal pattern was different especially during the weeks 0-3. These effects were reversed by IMI. An increase in the dopaminergic and a decrease in the serotonergic activity were observed in the prefrontal cortex in both rat strains following CMS. A decrease in the striatal dopaminergic activity and an increased hippocampal serotonergic activity were also seen in both rat strains following CMS. In Wistar rats, dopaminergic and serotonergic activities were enhanced in the hypothalamus whereas in Sprague-Dawley rats no such stress-induced changes were observed. Notably, the clear decrease in sucrose consumption observed in stressed Wistar rats could be directly associated with a respective increase in the dopaminergic hypothalamic activity. Chronic treatment with imipramine normalized all neurochemical alterations induced by CMS. Our results suggest that a specific and regionally differentiated serotonin-dopamine interaction is directly related to the observed stress-induced anhedonia. (c) 2005 Published by Elsevier B.V.