Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement
Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement
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DOI：
10.7554/elife.39945
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发表时间：
2018-10-30
期刊：
影响因子：
7.7
通讯作者：
Luescher, Christian
中科院分区：
文献类型：
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作者：
Corre, Julie;van Zessen, Ruud;Luescher, Christian
多巴胺（DA）假说假定中脑边缘多巴胺水平的增加是成瘾药物的定义共性，最初引起强化，最终导致强迫性消费。虽然许多来自精神兴奋剂的实验证据支持这一假设，但阿片类药物的强化作用受到了挑战。在这里，我们监测遗传编码的DA和钙指标以及cFos在小鼠中揭示，海洛因激活DA神经元位于腹侧被盖区的内侧部分，优先投射到内侧壳核（NAc）。化学遗传学和光遗传学操纵腹侧被盖区DA或GABA神经元建立了因果关系海洛因强化。抑制DA神经元阻断海洛因自我管理，而海洛因抑制DA神经元的光遗传学自我刺激。同样，海洛因封闭VTA GABA神经元的自我抑制。总之，这些实验支持模型的一个子集的腹侧被盖区DA神经元阿片类药物强化的去抑制。
The dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we monitor genetically encoded DA and calcium indicators as well as cFos in mice to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.