Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens
Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens
复制标题
伏隔核深部脑刺激期间酒精依赖大鼠出现矛盾性增强的复发性饮酒行为
DOI：
10.1038/tp.2016.100
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发表时间：
2016-06-21
影响因子：
6.8
通讯作者：
Winter, C.
中科院分区：
文献类型：
--
作者：
Hadar, R.;Vengeliene, V.;Winter, C.
病例报告表明，伏隔核脑深部刺激可能对酒精依赖患者有益。由于缺乏临床试验，加上我们对脑深部刺激的了解有限，需要进行转化性实验来验证这些报告。为了模拟人类的情况，我们使用了一种针对伏隔核和其他大脑部位的慢性持续脑刺激范式，在酒精依赖大鼠中进行。为了确定酒精依赖大鼠深部脑刺激的网络效应，我们将电刺激伏隔核与功能磁共振成像(FMRI)相结合，研究了伏隔核电刺激与假刺激大鼠的神经递质水平。令人惊讶的是，我们在这里报告说，伏隔核的电刺激导致酒精依赖大鼠复发行为的增加。我们的相关fMRI数据显示了一些激活的区域，包括内侧前额叶皮质和尾壳核。然而，当我们对这些区域进行刺激时，复发行为并没有受到影响，这证实了伏隔核是产生这种矛盾效应的关键。对该网络主要激活的大脑部位进行的神经化学分析显示，刺激的效果可能取决于伏隔多巴胺水平。与假刺激动物相比，脑刺激治疗的大鼠表现出酒精诱导的多巴胺释放增加，这一发现支持了这一点。我们的数据表明，伏隔核的脑深部刺激可能通过增加多巴胺的释放来增强对酒精的喜好，从而促进复发。
Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse.