Ventral pallidum DRD3 potentiates a pallido-habenular circuit driving accumbal dopamine release and cocaine seeking.
Ventral pallidum DRD3 potentiates a pallido-habenular circuit driving accumbal dopamine release and cocaine seeking.
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DOI：
10.1016/j.neuron.2021.05.002
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发表时间：
2021-07-07
期刊：
影响因子：
16.2
通讯作者：
Lim, Byung Kook
中科院分区：
文献类型：
--
作者：
Pribiag, Horia;Shin, Sora;Wang, Eric Hou-Jen;Sun, Fangmiao;Datta, Paul;Okamoto, Alexander;Guss, Hayden;Jain, Akanksha;Wang, Xiao-Yun;De Freitas, Bruna;Honma, Patrick;Pate, Stefan;Lilascharoen, Varoth;Li, Yulong;Lim, Byung Kook
滥用药物会导致奖赏回路功能的持续重塑--这一过程被认为是出现对药物的渴望和对药物依赖的基础。然而，电路特异的、药物诱导的分子和细胞可塑性如何在中脑边缘多巴胺奖励系统中产生分布效应，以促进药物复吸，目前还没有完全阐明。在这里，我们证明了腹侧苍白球(VP)中依赖于多巴胺受体D3(DRD3)的可塑性驱动了伏隔核多巴胺释放的增强，在戒断后寻求可卡因的复发中。我们发现，投射到外侧缰核(LHb)或腹侧被盖区(VTA)的两个不同的VP-DRD3+神经元群体在戒毒过程中显示出不同的活动模式，并且选择性地抑制LHb投射群体中升高的活动或DRD3信号会减少药物寻求。总之，我们的结果揭示了电路特异性DRD3介导的可塑性如何有助于药物复发的过程。Pribiag等人。结果表明，腹侧苍白球多巴胺受体D3信号通过激活投射到外侧缰核的神经元亚群来调节长期戒断可卡因后的药物寻找。在药物寻找过程中，这种调节反馈影响伏核外侧壳中多巴胺的释放。
Drugs of abuse induce persistent remodeling of reward circuit function – a process thought to underlie the emergence of drug craving and relapse to drug use. However, how circuit-specific, drug-induced molecular and cellular plasticity can have distributed effects on the mesolimbic dopamine reward system to facilitate relapse to drug use is not fully elucidated. Here, we demonstrate that dopamine receptor D3 (DRD3)-dependent plasticity in the ventral pallidum (VP) drives potentiation of dopamine release in the nucleus accumbens during relapse to cocaine seeking after abstinence. We show that two distinct VP DRD3+ neuronal populations projecting to either the lateral habenula (LHb) or the ventral tegmental area (VTA) display different patterns of activity during drug seeking following abstinence from cocaine self-administration, and that selective suppression of elevated activity or DRD3 signaling in the LHb-projecting population reduces drug seeking. Together, our results uncover how circuit-specific DRD3-mediated plasticity contributes to the process of drug relapse. Pribiag et al. show that ventral pallidum dopamine receptor D3 signaling regulates drug seeking following prolonged abstinence from cocaine self-administration, via activation of a subpopulation of neurons projecting to the lateral habenula. This regulation feeds back to influence dopamine release in the lateral shell of the nucleus accumbens during drug seeking.
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