Evidence map›Paper›PMID 40239651›Full record

ArticleNeuron2025

Dynorphin modulates reward-seeking actions through a pallido-amygdala cholinergic circuit.

Qingtao Sun, Mingzhe Liu, Wuqiang Guan, Xiong Xiao, Chunyang Dong, Michael R Bruchas, Larry S Zweifel, Yulong Li, Lin Tian, Bo Li

Abstract read
In one paragraph

Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Qingtao SunCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: qsun@cshl.edu.
Mingzhe LiuCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Wuqiang GuanCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Xiong XiaoCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Institute of Neuroscience, Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
Chunyang DongDepartment of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Michael R BruchasDepartment of Anesthesiology & Pain Medicine, University of Washington, Seattle, WA 98195, USA.
Larry S ZweifelDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, USA.
Yulong LiState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China.
Lin TianDepartment of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, CA, USA; Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.
Bo LiCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Funding

University of Washington Center of Excellence in Opioid Addiction ResearchP30DA048736 · NIDA · UNIVERSITY OF WASHINGTON · PI Charles Chavkin · 2019 to 2026
$13.0M
The basal ganglia–habenula circuitry in reward processingR01MH108924 · NIMH · COLD SPRING HARBOR LABORATORY · PI Jessica Tollkuhn · 2015 to 2026
$6.8M
NIDA NIH HHS P30 DA048736NIMH NIH HHS R01 MH108924
6 · The paper itself

Abstract

The endogenous opioid peptide dynorphin and its receptor κ-opioid receptor (KOR) have been implicated in divergent behaviors, but the underlying mechanisms remain elusive. Here, we show that dynorphin released from nucleus accumbens dynorphinergic neurons exerts powerful modulation over a ventral pallidum (VP) disinhibitory circuit, thereby controlling cholinergic transmission to the amygdala and reward-seeking behavior in mice. On one hand, dynorphin acts postsynaptically via KORs on VP GABAergic neurons to promote disinhibition of cholinergic neurons, which release acetylcholine into the amygdala to facilitate learning and invigorate actions. On the other hand, dynorphin also acts presynaptically via KORs on dynorphinergic terminals to limit its own release. Such autoinhibition keeps cholinergic neurons from prolonged activation and release of acetylcholine and prevents perseverant reward seeking. Our study reveals how dynorphin exquisitely modulates behavior through the cholinergic system and provides an explanation for why these neuromodulators are involved in motivational disorders, including depression and addiction.

Indexed as

AmygdalaBasal ForebrainCholinergic NeuronsDynorphinsRewardAcetylcholineAnimalsMaleMiceMice, Inbred C57BLNeural PathwaysNucleus AccumbensReceptors, Opioid, kappaAcetylcholineDynorphinsReceptors, Opioid, kappaacetylcholinebasolateral amygdaladynorphinkappa opioid receptormotivationnucleus accumbensventral pallidum

Identifiers

PMID40239651
PMCPMC12640778

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.