Evidence map›Paper›PMID 37285896›Full record

ArticleBiological psychiatry2023

Mu Opioid Receptor-Expressing Neurons in the Dorsal Raphe Nucleus Are Involved in Reward Processing and Affective Behaviors.

Lola Welsch, Esther Colantonio, Mathilde Frison, Desiree A Johnson, Shannan P McClain, Victor Mathis, Matthew R Banghart, Sami Ben Hamida, Emmanuel Darcq, Brigitte L Kieffer

Open access · greenAbstract read
In one paragraph

Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
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

14 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Dorsal raphe nucleus enkephalin peptide modulates behavioral preference.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Lola WelschDouglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada; INSERM U1114, Department of Psychiatry, University of Strasbourg, Strasbourg, France.
Esther ColantonioINSERM U1114, Department of Psychiatry, University of Strasbourg, Strasbourg, France.
Mathilde FrisonDouglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada.
Desiree A JohnsonNeurobiology Department, School of the Biological Sciences, University of California San Diego, La Jolla, California.
Shannan P McClainNeurobiology Department, School of the Biological Sciences, University of California San Diego, La Jolla, California.
Victor MathisCentre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, UPR 3212, Strasbourg, France.
Matthew R BanghartNeurobiology Department, School of the Biological Sciences, University of California San Diego, La Jolla, California.
Sami Ben HamidaDouglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada; INSERM UMR 1247, Université de Picardie Jules Verne, Amiens, France.
Emmanuel DarcqDouglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada; INSERM U1114, Department of Psychiatry, University of Strasbourg, Strasbourg, France.
Brigitte L KiefferDouglas Research Center, Department of Psychiatry, McGill University, Montréal, Quebec, Canada; INSERM U1114, Department of Psychiatry, University of Strasbourg, Strasbourg, France. Electronic address: brigitte.kieffer@unistra.fr.
Inserm · FRUniversity of California San Diego · USInstitut des Neurosciences Cellulaires et Intégratives · FRMcGill University · CA

Funding

The Role of Striosome Neurons in Mediating Opiod RewardP50DA005010 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WALWYN, WENDY M · 1987 to 2021
$30.7M
Morphine-responsive neurons of the medial habenula : a role in aversive states of morphine withdrawal ?R01DA048796 · NIDA · INSERM STRASBOURG · PI KIEFFER, BRIGITTE L. · 2020 to 2025
$1.4M
NIDA NIH HHS P50 DA005010NIDA NIH HHS R01 DA048796
6 · The paper itself

Abstract

backgroundMu opioid receptors (MORs) are key for reward processing, mostly studied in dopaminergic pathways. MORs are also expressed in the dorsal raphe nucleus (DRN), which is central for the modulation of reward and mood, but MOR function in the DRN remains underexplored. Here, we investigated whether MOR-expressing neurons of the DRN (DRN-MOR neurons) participate in reward and emotional responses.

methodsWe characterized DRN-MOR neurons anatomically using immunohistochemistry and functionally using fiber photometry in responses to morphine and rewarding/aversive stimuli. We tested the effect of opioid uncaging on the DRN on place conditioning. We examined the effect of DRN-MOR neuron optostimulation on positive reinforcement and mood-related behaviors. We mapped their projections and selected DRN-MOR neurons projecting to the lateral hypothalamus for a similar optogenetic experimentation.

resultsDRN-MOR neurons form a heterogeneous neuronal population essentially composed of GABAergic (gamma-aminobutyric acidergic) and glutamatergic neurons. Calcium activity of DRN-MOR neurons was inhibited by rewarding stimuli and morphine. Local photo-uncaging of oxymorphone in the DRN produced conditioned place preference. DRN-MOR neuron optostimulation triggered real-time place preference and was self-administered, promoted social preference, and reduced anxiety and passive coping. Finally, specific optostimulation of DRN-MOR neurons projecting to the lateral hypothalamus recapitulated the reinforcing effects of total DRN-MOR neuron stimulation.

conclusionsOur data show that DRN-MOR neurons respond to rewarding stimuli and that their optoactivation has reinforcing effects and promotes positive emotional responses, an activity which is partially mediated by their projections to the lateral hypothalamus. Our study also suggests a complex regulation of DRN activity by MOR opioids, involving mixed inhibition/activation mechanisms that fine-tune DRN function.

Indexed as

Dorsal Raphe NucleusReceptors, Opioid, muAnalgesics, OpioidMorphineNeuronsRewardAnalgesics, OpioidMorphineReceptors, Opioid, muDorsal raphe nucleusFiber photometryMouse behaviorOpioid circuitryOptogeneticsPositive affect

Identifiers

PMID37285896
PMCPMC10850692
OpenAlexW4379468559

What OpenQuestion 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 OpenQuestion graph.