Deep Brain Stimulation Reverses Anhedonic-Like Behavior in a Chronic Model of Depression: Role of Serotonin and Brain Derived Neurotrophic Factor
Deep Brain Stimulation Reverses Anhedonic-Like Behavior in a Chronic Model of Depression: Role of Serotonin and Brain Derived Neurotrophic Factor
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DOI：
10.1016/j.biopsych.2011.08.025
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发表时间：
2012-01-01
影响因子：
10.6
通讯作者：
Nobrega, Jose N.
中科院分区：
文献类型：
--
作者：
Hamani, Clement;Machado, Danilo C.;Nobrega, Jose N.
背景：脑深部刺激(DBS)是一种治疗重度抑郁症的方法，但其作用机制尚不清楚。我们研究了刺激腹内侧额叶皮质(VmPFC)在慢性抑郁症模型中的作用，并评估了5-羟色胺能系统和脑源性神经营养因子(BDNF)在DBS反应中的参与。方法：大鼠在4周内受到慢性不可预测的轻度应激。每周监测一次对蔗糖溶液而不是水的偏好的下降，这一指数被认为是反映非享乐性行为的指数。单独的慢性vmPFC刺激(每天8小时，持续2周)或合并5-羟色胺耗竭损伤的结果是有特征的。结果：与对照组相比，应激组大鼠海马区脑源性神经营养因子水平和对蔗糖的偏好性显著降低。刺激vmPFC可完全逆转这一行为缺陷，并部分增加BDNF水平。相反，DBS不能改善5-羟色胺耗竭中缝损伤动物的应激诱导的类享乐行为，而海马区BDNF水平相关正常。结论：刺激vmPFC对慢性抑郁症模型有效。我们的结果表明，5-羟色胺能系统的完整性对于DBS的抗快乐样作用是重要的，但对海马区BDNF的直接作用提出了质疑。
Background: Deep brain stimulation (DBS) is being investigated as a treatment for major depression, but its mechanisms of action are still unknown. We have studied the effects of ventromedial prefrontal cortex (vmPFC) stimulation in a chronic model of depression and assessed the involvement of the serotonergic system and brain derived neurotrophic factor (BDNF) in a DBS response.Methods: Rats were subjected to chronic unpredictable mild stress during 4 weeks. Decline in preference for sucrose solutions over water, an index suggested to reflect anhedonic-like behavior, was monitored on a weekly basis. The outcome of chronic vmPFC stimulation alone (8 hours/day for 2 weeks) or combined with serotonin-depleting lesions was characterized. BDNF levels were measured in the hippocampus.Results: Stress induced a significant decrease in sucrose preference as well as hippocampal BDNF levels as compared with those recorded in control subjects. vmPFC stimulation completely reversed this behavioral deficit and partially increased BDNF levels. In contrast, DBS did not improve stress-induced anhedonic-like behavior in animals bearing serotonin-depleting raphe lesions with associated normal hippocampal BDNF levels.Conclusions: vmPFC stimulation was effective in a chronic model of depression. Our results suggest that the integrity of the serotonergic system is important for the anti-anhedonic-like effects of DBS but question a direct role of hippocampal BDNF.