Medial Forebrain Bundle Deep Brain Stimulation has Symptom-specific Anti-depressant Effects in Rats and as Opposed to Ventromedial Prefrontal Cortex Stimulation Interacts With the Reward System
Medial Forebrain Bundle Deep Brain Stimulation has Symptom-specific Anti-depressant Effects in Rats and as Opposed to Ventromedial Prefrontal Cortex Stimulation Interacts With the Reward System
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DOI：
10.1016/j.brs.2015.02.009
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发表时间：
2015-07-01
影响因子：
7.7
通讯作者：
Winter, Christine
中科院分区：
文献类型：
--
作者：
Edemann-Callesen, Henriette;Voget, Mareike;Winter, Christine
背景：近年来，脑深部刺激(DBS)已成为治疗难治性抑郁症(TRD)患者的一种有前途的治疗选择。几个刺激靶点已在临床环境中成功测试，包括膝下扣带(Cg25)和内侧前脑束(MFB)。MFB-DBS取得了显著的效果，在响应延迟和响应者数量方面超过了以前的目标。目的/假设：本研究的目的是深入研究MFB-DBS在Flinders敏感线(Flinders Sensitive Line，FSL)大鼠抑郁模型中的抗抑郁作用，以及MFB-DBS和Cg25-DBS是否通过相同的神经生物学回路发挥作用。方法：FFB-DBS和对照组大鼠在下丘脑外侧水平接受双侧MFB的高频刺激，同时受到各种抑郁和焦虑相关行为范式的影响。为了进一步比较MFB-DBS和Cg25-DBS对奖赏相关行为的影响，动物被刺激在MFB或类似于Cg25的大鼠腹内侧前额叶皮质(VmPFC)，同时接受颅内自我刺激范式的测试。结果：MFB-DBS具有明显的症状特异性抗抑郁作用。ICSS范式显示，与vmPFC-DBS不同，MFB-DBS与奖赏系统相互作用。结论：MFB-DBS和Cg25-DBS通过不同的神经生物学回路起作用。在选择Cg25-DBS或MFB-DBS患者时，这种区别可能是有意义的。(C)2015 Elsevier Inc.保留所有权利。
Background: In recent years, deep brain stimulation (DBS) has emerged as a promising treatment option for patients suffering from treatment-resistant depression (TRD). Several stimulation targets have successfully been tested in clinical settings, including the subgenual cingulum (Cg25) and the medial forebrain bundle (MFB). MFB-DBS has led to remarkable results, surpassing the effect of previous targets in terms of response latency and number of responders. However, the question remains as to which mechanisms underlie this difference.Objective/hypothesis: The aim of the present study was to thoroughly study the anti-depressant effect of MFB-DBS in the Flinders sensitive line (FSL) rat model of depression as well as to investigate whether MFB-DBS and Cg25-DBS operate through the same neurobiological circuits.Methods: FSL and control rats received bilateral high-frequency stimulation to the MFB at the level of the lateral hypothalamus, while being subjected to a variety of depression-and anxiety-related behavioral paradigms. To further compare the effects of MFB-DBS and Cg25-DBS on reward-related behavior, animals were stimulated in either the MFB or ventromedial prefrontal cortex (vmPFC, rodent analog to Cg25), while being tested in the intra-cranial self-stimulation paradigm.Results: A marked symptom-specific anti-depressant effect of MFB-DBS was demonstrated. The ICSS-paradigm revealed that MFB-DBS, as opposed to vmPFC-DBS interacts with the reward system.Conclusion: Our data suggest that MFB-DBS and Cg25-DBS do not operate via the same neurobiological circuits. This differentiation might be of interest when selecting patients for either Cg25- or MFB-DBS. (C) 2015 Elsevier Inc. All rights reserved.