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首页> 外文期刊>Neuron >Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction
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Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction

机译：中脑边缘多巴胺神经元刺激的成瘾进展的充分性。

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The factors causing the transition from recreational drug consumption to addiction remain largely unknown. It has not been tested whether dopamine (DA) is sufficient to trigger this process. Here we use optogenetic self-stimulation of DA neurons of the ventral tegmental area (VTA) to selectively mimic the defining commonality of addictive drugs. All mice readily acquired self-stimulation. After weeks of abstinence, cue-induced relapse was observed in parallel with a potentiation of excitatory afferents onto D1 receptor-expressing neurons of the nucleus accumbens (NAc). When the mice had to endure a mild electric foot shock to obtain a stimulation, some stopped while others persevered. The resistance to punishment was associated with enhanced neural activity in the orbitofrontal cortex (OFC) while chemogenetic inhibition of the OFC reduced compulsivity. Together, these results show that stimulating VTA DA neurons induces behavioral and cellular hallmarks of addiction, indicating sufficiency for the induction and progression of the disease.
机译：从消遣性毒品消费向成瘾过渡的因素在很大程度上仍然未知。尚未测试多巴胺（DA）是否足以触发该过程。在这里，我们使用腹侧被盖区（VTA）的DA神经元的光遗传自我刺激来选择性地模仿成瘾性药物的定义通用性。所有小鼠都容易获得自我刺激。禁欲几周后，观察到提示诱导的复发，同时在伏隔核（NAc）的表达D1受体的神经元上兴奋性传入增强。当老鼠不得不忍受轻微的脚底电击以获得刺激时，一些老鼠停下来了，而另一些则坚持了下来。对惩罚的抵抗力与眶额皮质（OFC）的神经活动增强有关，而对OFC的化学生成抑制作用降低了强迫性。在一起，这些结果表明，刺激VTA DA神经元会诱导成瘾的行为和细胞特征，表明该疾病的诱导和进展是足够的。

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