Ventral Pallidum DRD3 Potentiates a Pallido-habenular Circuit Driving Accumbal Dopamine Release and Cocaine Seeking

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2021 May 28

PMID 34048697

Citations 33

Authors

Horia Pribiag

Sora Shin

Eric Hou-Jen Wang

Fangmiao Sun

Paul Datta

Alexander Okamoto

Hayden Guss

Akanksha Jain

Xiao-Yun Wang

Bruna De Freitas

Patrick Honma

Stefan Pate

Varoth Lilascharoen

Yulong Li

Byung Kook Lim

Affiliations

Soon will be listed here.

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.

Citing Articles

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Transcriptomic landscape of mammalian ventral pallidum at single-cell resolution.

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