A ventral pallidal glutamatergic aversive network encodes abstinence from and reexposure to cocaine

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-07-23 DOI:10.1126/sciadv.adu6074

Liran A. Levi, Kineret Inbar, Esti Tseiger, Yonatan M. Kupchik

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Abstract

Relapse to drugs of abuse can occur after long periods of abstinence. The ventral pallidum (VP) is central to drug addiction, and its glutamatergic neurons (VP_Glu), whose activation drives aversion, inhibit drug seeking. However, it remains unknown whether these neurons encode the abstinence from and relapse to drugs. We show here that VP_Glu projections specifically to the aversion-related lateral habenula (LHb) and ventral tegmental area gabaergic (VTA_GABA) neurons show plasticity induced by abstinence from and reexposure to cocaine or cocaine cues. Both these pathways potentiate during abstinence and restore baseline values upon drug reexposure but with different plasticity mechanisms. Last, inhibiting the VP_Glu → LHb pathway enhances cocaine preference after abstinence, while inhibiting the VP_Glu → VTA pathway shows variable effects. These findings establish an aversive circuit orchestrated by VP_Glu neurons encoding long-term abstinence-driven changes that may contribute to drug relapse.

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腹侧苍白部谷氨酸能厌恶网络编码对可卡因的戒断和再暴露

在长时间的戒断之后，可能会再次滥用药物。腹侧白质（VP）是药物成瘾的中心，其谷氨酸能神经元（VP Glu）的激活导致厌恶，抑制药物寻求。然而，尚不清楚这些神经元是否对药物的戒断和复发进行编码。我们在这里发现，VP Glu特异地投射到与厌恶相关的外侧链（LHb）和腹侧被盖区gabaergic （VTA GABA）神经元上，显示出戒断和再次暴露于可卡因或可卡因线索所诱导的可塑性。这两种途径都在戒断期间增强，并在再次接触药物时恢复基线值，但具有不同的可塑性机制。最后，抑制VP Glu→LHb通路可增强戒毒后的可卡因偏好，而抑制VP Glu→VTA通路则表现出不同的效果。这些发现建立了一个由VP Glu神经元精心策划的厌恶回路，编码长期戒断驱动的变化，可能有助于药物复发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.