Evidence map›Paper›PMID 42024504›Full record

ArticleCell reports2026

Midbrain endocannabinoids actuate dopamine-based action selection.

M Á Luján, R Young-Morrison, V Kashtelyan, G Loewinger, Tanner D Klingenberg, A F Hoffman, I Gildish, D P Covey, E E McDonnell, F Morgado and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. 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. Review
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

15 authors.

M Á LujánDepartment of Anatomy and Cell Biology, University of Illinois College of Medicine, Chicago, IL, USA; Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
R Young-MorrisonDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
V KashtelyanNeuronal Networks Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
G LoewingerMachine Learning Core, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Tanner D KlingenbergElectrophysiology Research Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
A F HoffmanElectrophysiology Research Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
I GildishDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
D P CoveyDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Lovelace Biomedical Research Institute, Albuquerque, NM, USA.
E E McDonnellDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
F MorgadoDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
K PetersDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
A Y KimDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
F PereiraMachine Learning Core, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
C R LupicaElectrophysiology Research Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.
J F CheerDepartment of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: jcheer@som.umaryland.edu.

Funding

Endogenous Cannabinoid Control of Reward SubstratesR01DA022340 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI Joseph F Cheer · 2008 to 2026
$5.6M
NIDA NIH HHS R01 DA022340
6 · The paper itself

Abstract

Quickly adapting behavior to changing environments is key for survival. Brain dopamine signals reinforce actions that procure rewards and avoid adverse outcomes. However, the molecular mechanisms within the circuits that actuate these signals at subsecond timescales remain unexplored. We show that midbrain endocannabinoid mobilization is the conditio sine qua non for behavioral invigoration evoked by external cues. Reward- and punishment-predictive signals require intact retrograde release of the endocannabinoid 2-arachidonoylglycerol (2-AG) from ventral tegmental area dopamine neurons. Moreover, we show that genetic deletion of presynaptic cannabinoid type-1 receptors (CB1Rs), the target for 2-AG, recapitulates behavioral and dopaminergic deficits. Exploiting causal inference tools to interpret continuous brain signals, we describe that 2-AG/CB1R communication is essential for striatal dopamine release to signal salient cues and propel conditioned responding. These findings reveal an endocannabinoid-mediated disinhibition mechanism exploited by dopamine neurons to orchestrate striatal dopamine release events, enabling adaptive action selection informed by cues.

Indexed as

DopamineEndocannabinoidsMesencephalonAnimalsArachidonic AcidsDopaminergic NeuronsGlyceridesMaleMiceMice, Inbred C57BLReceptor, Cannabinoid, CB1RewardVentral Tegmental AreaArachidonic AcidsDopamineEndocannabinoidsGlyceridesglyceryl 2-arachidonateReceptor, Cannabinoid, CB1avoidancecannabinoidsconditioningCP: neurosciencedopamineescapemidbrainmotivationpallidum

Identifiers

PMID42024504
PMCPMC13285665

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.