Evidence map›Paper›PMID 26903621›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence.

Natalie Hirth, Marcus W Meinhardt, Hamid R Noori, Humberto Salgado, Oswaldo Torres-Ramirez, Stefanie Uhrig, Laura Broccoli, Valentina Vengeliene, Martin Roßmanith, Stéphanie Perreau-Lenz and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 5 pooled it
11.1field-weighted citation impact, top 1% 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

90 citing papers in PubMed, 5 syntheses or guidelines pooled it, 136 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Pooled it
  4. Inhalation of Alcohol Vapor: Measurement and Implications.Alcoholism, clinical and experimental research · 2017
    Pooled it
  5. Pooled it
  6. Trial
  7. Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Trial
  8. Dopamine Transporter and Reward Anticipation in a Dimensional Perspective: A Multimodal Brain Imaging Study.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Trial
  9. Low μ-Opioid Receptor Status in Alcohol Dependence Identified by Combined Positron Emission Tomography and Post-Mortem Brain Analysis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017
    Trial
  10. Article
  11. Article
  12. Review
  13. Article
  14. Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder.Basic & clinical pharmacology & toxicology · 2025
    Review
  15. Review
  16. The Dopamine System in Mediating Alcohol Effects in Humans.Current topics in behavioral neurosciences · 2025
    Review
  17. Molecular Imaging Studies of Alcohol Use Disorder.Current topics in behavioral neurosciences · 2025
    Review
  18. Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025
    Review
  19. Review
  20. Review

30 more citing papers are in PubMed but not listed here.

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

14 authors at 4 institutions in 2 countries.

Natalie HirthInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Marcus W MeinhardtInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Hamid R NooriInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Humberto SalgadoNeurosciences Department, Autonomous University of Yucatán, 97000 Merida, Yucatan, Mexico;
Oswaldo Torres-RamirezNeurosciences Department, Autonomous University of Yucatán, 97000 Merida, Yucatan, Mexico;
Stefanie UhrigInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Laura BroccoliInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Valentina VengelieneInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Martin RoßmanithInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Stéphanie Perreau-LenzInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Georg KöhrInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Wolfgang H SommerInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany; Department of Addictive Behavior and Addiction Medicine at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
Rainer SpanagelInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany;
Anita C HanssonInstitute for Psychopharmacology at Central Institute for Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany; anita.hansson@zi-mannheim.de.
University Hospital Heidelberg · DECentral Institute of Mental Health · DEHeidelberg University · DEAutonomous University of Yucatán · MX

Funding

Brain Tissue Resource Centre for Alcohol ResearchR28AA012725 · NIAAA · UNIVERSITY OF SYDNEY · PI Greg Trevor Sutherland · 2012 to 2026
$7.0M
NIAAA NIH HHS R28 AA012725
6 · The paper itself

Abstract

A major hypothesis in addiction research is that alcohol induces neuroadaptations in the mesolimbic dopamine (DA) system and that these neuroadaptations represent a key neurochemical event in compulsive drug use and relapse. Whether these neuroadaptations lead to a hypo- or hyperdopaminergic state during abstinence is a long-standing, unresolved debate among addiction researchers. The answer is of critical importance for understanding the neurobiological mechanism of addictive behavior. Here we set out to study systematically the neuroadaptive changes in the DA system during the addiction cycle in alcohol-dependent patients and rats. In postmortem brain samples from human alcoholics we found a strong down-regulation of the D1 receptor- and DA transporter (DAT)-binding sites, but D2-like receptor binding was unaffected. To gain insight into the time course of these neuroadaptations, we compared the human data with that from alcohol-dependent rats at several time points during abstinence. We found a dynamic regulation of D1 and DAT during 3 wk of abstinence. After the third week the rat data mirrored our human data. This time point was characterized by elevated extracellular DA levels, lack of synaptic response to D1 stimulation, and augmented motor activity. Further functional evidence is given by a genetic rat model for hyperdopaminergia that resembles a phenocopy of alcohol-dependent rats during protracted abstinence. In summary, we provide a new dynamic model of abstinence-related changes in the striatal DA system; in this model a hyperdopaminergic state during protracted abstinence is associated with vulnerability for relapse.

Indexed as

Alcohol Abstinence3,4-Dihydroxyphenylacetic AcidAdultAgedAlcoholismAnimalsBenzazepinesBrain ChemistryDisease Models, AnimalDopamineDopamine Plasma Membrane Transport ProteinsEthanolExcitatory Postsynaptic PotentialsFemaleGene Expression RegulationHomovanillic Acid3,4-Dihydroxyphenylacetic AcidBenzazepinesDopamineDopamine Plasma Membrane Transport ProteinsDRD2 protein, humanEthanolHomovanillic AcidReceptors, Dopamine D1Receptors, Dopamine D2SK&F 81297alcoholismdopamine releasein silico analysispostmortem brain tissuetranslational studies

Identifiers

PMID26903621
PMCPMC4801269
OpenAlexW2285481902

What OpenQuestion holds

Textmetadata
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.