Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms.
Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms.
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DOI：
10.1038/tp.2015.24
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发表时间：
2015-03-31
影响因子：
6.8
通讯作者：
Temel Y
中科院分区：
文献类型：
--
作者：
Lim LW;Prickaerts J;Huguet G;Kadar E;Hartung H;Sharp T;Temel Y
脑深部电刺激（DBS）是治疗难治性抑郁症的一种有前途的治疗方法。然而，关键问题仍然是哪些大脑目标应该用于刺激，以及哪些机制是治疗效果的基础。在这里，我们研究了DBS的影响，低和高频率刺激（LFS，HFS），在不同的大脑区域（腹内侧前额叶皮层，vmPFC;扣带皮层，Cg;背核（NAc）的核心或壳;外侧缰核，LHb;和腹侧被盖区）对各种抑郁样行为使用大鼠模型。在幼稚动物研究中，我们发现Cg，vmPFC，NAc核心和LHb的HFS降低了焦虑水平，增加了食物的动机。在慢性不可预测的压力模型中，有一个强大的抑郁样行为表型。此外，vmPFC HFS，在所有刺激目标的比较，产生了最深刻的抗抑郁作用，增强快感，减少焦虑和减少强迫游泳不动。在下面的一组电生理和组织化学实验，旨在解开一些潜在的机制，我们发现，vmPFC HFS引起中缝背核（DRN），这一直与情绪的多巴胺能神经元的特定调制。最后，通过c-Fos表达的神经元映射方法，我们发现vmPFC HFS调制与DRN相关的脑回路，并且已知参与影响。总之，HFS的vmPFC产生最有效的抗抑郁作用，在幼稚大鼠和大鼠受到的机制，也包括DRN的压力。
Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.
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影响因子：
4.8
作者：
Falowski SM;Sharan A;Reyes BA;Sikkema C;Szot P;Van Bockstaele EJ
通讯作者：
Van Bockstaele EJ
影响因子：
10.6
作者：
Hamani, Clement;Machado, Danilo C.;Nobrega, Jose N.
通讯作者：
Nobrega, Jose N.
影响因子：
5.6
作者：
Araragi, Naozumi;Mlinar, Boris;Corradetti, Renato
通讯作者：
Corradetti, Renato
影响因子：
16.2
作者：
Euston DR;Gruber AJ;McNaughton BL
通讯作者：
McNaughton BL
影响因子：
4.7
作者：
Hajós, M;Gartside, SE;Sharp, T
通讯作者：
Sharp, T