Evidence map›Paper›PMID 42673964›Full record

ArticleCell2026

Endogenous opioid dynamics in the dorsal striatum sculpt neural activity to promote goal-directed action.

Raajaram Gowrishankar, Madelyn M Hjort, Abigail J Elerding, Sofia E Shirley, Pranav Senthilkumar, Josie Van Tilburg, David J Marcus, Khalid A Abrera, Dustin Sumarli, Marcelina Wezik and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. BLAbioRxiv : the preprint server for biology · 2024
    Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Raajaram GowrishankarDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center for the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, USA. Electronic address: gowrisha@musc.edu.
Madelyn M HjortDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Neuroscience Graduate Program, University of Washington, Seattle, WA, USA.
Abigail J ElerdingDepartment of Pharmacology, University of Washington, Seattle, WA, USA.
Sofia E ShirleyDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
Pranav SenthilkumarDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
Josie Van TilburgDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
David J MarcusDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center for the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, USA.
Khalid A AbreraDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
Dustin SumarliDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
Marcelina WezikDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
Kat MotovilovDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
Adam G GordonDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center for the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, USA.
Zhe C ZhouDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center for the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, USA.
Chunyang DongDepartment of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA.
Lin TianDepartment of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA; Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.
Garret D StuberDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center for the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA.
Michael R BruchasDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA; Center for the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA, USA; Department of Pharmacology, University of Washington, Seattle, WA, USA. Electronic address: mbruchas@uw.edu.

Funding

Project 4_Bruchas : Circuit-level Approaches for Dissecting Approach/Avoidance Behaviors Mediated by Nociceptin Systems in MiceP50MH119467 · NIMH · MCLEAN HOSPITAL · PI PIZZAGALLI, DIEGO A · 2020 to 2024
$15.9M
University of Washington Center of Excellence in Opioid Addiction ResearchP30DA048736 · NIDA · UNIVERSITY OF WASHINGTON · PI Charles Chavkin · 2019 to 2026
$13.0M
Neural circuit elements that orchestrate cue-reward associationsR37DA032750 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Garret D Stuber · 2017 to 2026
$4.5M
DISSECTING DYNORPHIN-KAPPA OPIOID MEDIATED REINSTATEMENT OF NICOTINE PREFERENCER37DA033396 · NIDA · WASHINGTON UNIVERSITY · PI Michael R. Bruchas · 2018 to 2026
$3.8M
Elucidating the role of the endogenous opioid dynorphin in reward seekingK99DA058709 · NIDA · UNIVERSITY OF WASHINGTON · PI GOWRISHANKAR, RAAJARAM · 2023 to 2024
$349k
Multimodal Sensory Integration in Orbitofrontal Cortex during Natural Reward SeekingF31DA053706 · NIDA · UNIVERSITY OF WASHINGTON · PI HJORT, MADELYN · 2022 to 2024
$126k
NIDA NIH HHS F31 DA053706NIDA NIH HHS K99 DA058709NIDA NIH HHS P30 DA048736NIDA NIH HHS R37 DA032750NIDA NIH HHS R37 DA033396NIMH NIH HHS P50 MH119467
6 · The paper itself

Abstract

Endogenous neuropeptides are uniquely poised to regulate neuronal activity and behavior across multiple timescales. Traditional studies ascribing neuropeptide contributions to behavior lack spatiotemporal precision. The endogenous opioid dynorphin is a neuropeptide highly enriched in the dorsal striatum, a region critical for goal-directed behavior. However, the functional role of endogenous dynorphin- kappa opioid receptor (KOR) signaling in goal-directed behavior is unknown. Here, we report that local, time-locked dynorphin release from dorsomedial striatum medium spiny neurons (MSNs) is necessary and sufficient for goal-directed behavior using a suite of modern approaches, including conditional deletions, neuropeptide biosensor detection, two-photon imaging, and time-locked optogenetic manipulations of neuropeptide release. We discovered that glutamatergic axon terminals from the basolateral amygdala evoke striatal dynorphin release, resulting in feed-forward retrograde presynaptic G protein-coupled receptor (GPCR) inhibition to promote behavior. Collectively, our findings isolate a causal role for endogenous neuropeptide release at rapid timescales and subsequent pre-synaptic Gi-GPCR activity for promoting goal-directed behavior.

Indexed as

Corpus StriatumDynorphinsAnimalsGoalsMaleMedium Spiny NeuronsMiceMice, Inbred C57BLNeuronsNeuropeptidesOptogeneticsReceptors, G-Protein-CoupledReceptors, Opioid, kappaDynorphinsNeuropeptidesReceptors, G-Protein-CoupledReceptors, Opioid, kappadorsal striatumdynorphingoal-directed behaviorin vivo fiber photometryin vivo two-photon calcium imagingkappa opioid receptorneuropeptidesopioids

Identifiers

PMID42673964
PMCPMC13637798

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.