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University of California, San Diego

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Neuron, Published: May 27, 2021 | https://doi.org/10.1016/j.neuron.2021.05.002 Ventral pallidum DRD3 potentiates a pallido-habenular circuit driving accumbal dopamine release and cocaine seeking

Horia Pribiag,¹ Sora Shin,^1,2,3 Eric Hou-Jen Wang,^1,4 Fangmiao Sun,^5,6 Paul Datta,¹ Alexander Okamoto,¹ Hayden Guss,¹ Akanksha Jain,¹ Xiao-Yun Wang,¹ Bruna De Freitas,¹ Patrick Honma,¹ Stefan Pate,¹ Varoth Lilascharoen,^1,7 Yulong Li,^5,6 and Byung Kook Lim^1,4,7,8,*

¹Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA
²Center for Neurobiology Research, Fralin Biomedical Research Institute at Virginia Tech Carilion, Virginia Tech, Roanoke, VA 24016, USA
³Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA 24061, USA
⁴Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
⁵State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, 100871 10 Beijing, China
⁶PKU-IDG/McGovern Institute for Brain Research, 100871 Beijing, China
⁷Biological Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA
⁸Lead contact

^*Correspondence

Abstract

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.

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형식Research article
게재일2021년 05월 (BRIC 등록일 2021-09-24)
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