The Effects of Fluoxetine Treatment in a Chronic Mild Stress Rat Model on Depression-Related Behavior, Brain Neurotrophins and ERK Expression
The Effects of Fluoxetine Treatment in a Chronic Mild Stress Rat Model on Depression-Related Behavior, Brain Neurotrophins and ERK Expression
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DOI：
10.1007/s12031-011-9515-5
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发表时间：
2011-10-01
影响因子：
3.1
通讯作者：
Weizman, Abraham
中科院分区：
文献类型：
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作者：
First, Maya;Gil-Ad, Irit;Weizman, Abraham
抑郁症与海马体（HC）体积减少有关。大鼠的慢性轻度应激（CMS）是抑郁症的模型。抗抑郁药可减轻 HC 容量损失并逆转应激动物的抑郁样症状。我们评估了 CMS 和选择性血清素再摄取抑制剂氟西汀 (FLX) 治疗对大鼠行为和认知参数以及 HC 和额叶皮层 (FC) 神经营养因子水平的影响。雄性大鼠在 5 周内连续暴露于各种温和的压力源。将 FLX（5 毫克/公斤/天，腹腔注射）给予应激组和对照组（无应激）。 CMS 5 周后，使用莫里斯水迷宫 (MWM) 对动物进行测试。在 MWM 中，我们观察到 FLX 对无压力的大鼠有短暂的影响。 CMS 降低了 HC 中的胰岛素样生长因子 1 受体 (IGF-1R) 水平，而 FLX 治疗后这些水平恢复到正常范围。 CMS 大鼠显示 HC 和 FC 区域的细胞外信号调节激酶 (ERK) 磷酸化显着降低，而 FLX 使这些水平正常化。这项研究表明 IGF-1R 和 ERK 可能在介导神经应激反应和 FLX 的作用模式中发挥作用。这个作用似乎与 BDNF 的改变无关。
Depression is associated with hippocampus (HC) volume loss. Chronic mild stress (CMS) in rats is a model of depression. Antidepressants attenuate HC volume loss and reverse the depression-like symptoms of stressed animals. We evaluated the effect of CMS and the selective serotonin reuptake inhibitor, fluoxetine (FLX) treatment on behavioral and cognitive parameters in rats, and on HC and frontal cortex (FC) neurotrophic factors levels. Male rats were exposed sequentially, over a period of 5 weeks, to a variety of mild stressors. FLX (5 mg/kg/day ip) was administered to the stressed group and controls (unstressed). After 5 weeks of CMS, animals were tested using the Morris Water Maze (MWM). In the MWM, we observed that FLX had a transitory effect on unstressed rats. CMS reduced insulin-like growth factor-1 receptor (IGF-1R) levels in the HC whereas after FLX treatment these levels reverted to normal range. CMS rats revealed a significant decrease in extracellular signal-regulated kinase (ERK) phosphorylation in both HC and FC regions, while FLX normalized these levels. This study suggests that IGF-1R and ERK may have a role in mediating the neural stress response and the mode of action of FLX. This role seems to be independent of the BDNF alterations.