Activation of mesocorticolimbic dopamine projections initiates cue-induced reinstatement of reward seeking in mice
Activation of mesocorticolimbic dopamine projections initiates cue-induced reinstatement of reward seeking in mice
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DOI：
10.1038/s41401-022-00866-x
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发表时间：
2022-02-25
影响因子：
8.2
通讯作者：
Song, Rui
中科院分区：
文献类型：
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作者：
Jing, Man-yi;Ding, Xiao-yan;Song, Rui
当成瘾者再次暴露于与药物相关的环境线索时，其特征是复发，但线索诱导复发的神经机制尚不清楚。在本研究中，我们研究了从腹侧被盖区（VTA）到伏隔核（NAcore）的特定多巴胺能（DA）通路在小鼠线索诱导的复发中的作用。在DAT-Cre转基因小鼠中建立了光学颅内自刺激（oICSS）。我们发现，VTA内的DA神经元或它们在NAcore、NAshell或边缘下前额叶皮层（PFC-IL）的投射终端的光遗传兴奋是有益的。此外，单独激活VTA-NAcore通路是诱导oICSS恢复的充分和必要条件。在可卡因自我给药模型中，通过细胞内GCaMP信号评估，可卡因相关线索激活了VTA DA神经元。线索诱导的可卡因寻求恢复是由VTA-NAcore途径的光遗传刺激触发的，并被该途径的化学发生抑制所抑制。总之，这些结果表明，线索诱导的寻求奖励的恢复在一定程度上是由VTA-NAcore DA通路的激活介导的。
Drug addiction is characterized by relapse when addicts are re-exposed to drug-associated environmental cues, but the neural mechanisms underlying cue-induced relapse are unclear. In the present study we investigated the role of a specific dopaminergic (DA) pathway from ventral tegmental area (VTA) to nucleus accumbens core (NAcore) in mouse cue-induced relapse. Optical intracranial self-stimulation (oICSS) was established in DAT-Cre transgenic mice. We showed that optogenetic excitation of DA neurons in the VTA or their projection terminals in NAcore, NAshell or infralimbic prefrontal cortex (PFC-IL) was rewarding. Furthermore, activation of the VTA-NAcore pathway alone was sufficient and necessary to induce reinstatement of oICSS. In cocaine self-administration model, cocaine-associated cues activated VTA DA neurons as assessed by intracellular GCaMP signals. Cue-induced reinstatement of cocaine-seeking was triggered by optogenetic stimulation of the VTA-NAcore pathway, and inhibited by chemogenetic inhibition of this pathway. Together, these results demonstrate that cue-induced reinstatement of reward seeking is in part mediated by activation of the VTA-NAcore DA pathway.