Evidence map›Paper›PMID 36170833›Full record

ArticleCell reports2022

Dopamine D2 receptors bidirectionally regulate striatal enkephalin expression: Implications for cocaine reward.

Kathy Z Dai, In Bae Choi, Ryan Levitt, Mariah B Blegen, Alanna R Kaplan, Aya Matsui, J Hoon Shin, Miriam E Bocarsly, Eleanor H Simpson, Christoph Kellendonk and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. 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
1.6field-weighted citation impact, top 18% 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, 18 citations in OpenAlex.

  1. Article
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  5. Activity-Dependent Regulation of Basal Forebrain Cholinergic Neurons by Striatal Spiny Projection Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
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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

12 authors at 4 institutions in 1 country.

Kathy Z DaiLaboratory on Neurobiology of Compulsive Behaviors, NIAAA, IRP, NIH, Bethesda, MD, USA.
In Bae ChoiDepartment of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Ryan LevittDepartment of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Mariah B BlegenLaboratory on Neurobiology of Compulsive Behaviors, NIAAA, IRP, NIH, Bethesda, MD, USA.
Alanna R KaplanLaboratory on Neurobiology of Compulsive Behaviors, NIAAA, IRP, NIH, Bethesda, MD, USA.
Aya MatsuiLaboratory on Neurobiology of Compulsive Behaviors, NIAAA, IRP, NIH, Bethesda, MD, USA.
J Hoon ShinLaboratory on Neurobiology of Compulsive Behaviors, NIAAA, IRP, NIH, Bethesda, MD, USA.
Miriam E BocarslyLaboratory on Neurobiology of Compulsive Behaviors, NIAAA, IRP, NIH, Bethesda, MD, USA; Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, Rutgers Brain Health Institute, Newark, NJ, USA.
Eleanor H SimpsonDepartment of Psychiatry, Columbia University Medical Center, New York, NY, USA; Division of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, USA.
Christoph KellendonkDepartment of Psychiatry, Columbia University Medical Center, New York, NY, USA; Department of Molecular Pharmacology and Therapeutics, Columbia University Medical Center, New York, NY, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA.
Veronica A AlvarezLaboratory on Neurobiology of Compulsive Behaviors, NIAAA, IRP, NIH, Bethesda, MD, USA; Center on Compulsive Behaviors, IRP, NIH, Bethesda, MD, USA.
Lauren K DobbsDepartment of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA; Department of Neuroscience, Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX, USA. Electronic address: ldobbs@austin.utexas.edu.
The University of Texas at Austin · USColumbia University Irving Medical Center · USNational Institutes of Health · USRutgers, The State University of New Jersey · US

Funding

Synaptic mechanisms underlying reward seeking and compulsive drug useZIAAA000421 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI ALVAREZ, VERONICA A · 2009 to 2025
$23.1M
Medium Spiny Neuron Excitability and MotivationR01MH093672 · NIMH · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI KELLENDONK, CHRISTOPH · 2011 to 2020
$5.0M
Intramural NIH HHS ZIA AA000421NIMH NIH HHS R01 MH093672
6 · The paper itself

Abstract

Low dopamine D2 receptor (D2R) availability in the striatum can predispose for cocaine abuse; though how low striatal D2Rs facilitate cocaine reward is unclear. Overexpression of D2Rs in striatal neurons or activation of D2Rs by acute cocaine suppresses striatal Penk mRNA. Conversely, low D2Rs in D2-striatal neurons increases striatal Penk mRNA and enkephalin peptide tone, an endogenous mu-opioid agonist. In brain slices, met-enkephalin and inhibition of enkephalin catabolism suppresses intra-striatal GABA transmission. Pairing cocaine with intra-accumbens met-enkephalin during place conditioning facilitates acquisition of preference, while mu-opioid receptor antagonist blocks preference in wild-type mice. We propose that heightened striatal enkephalin potentiates cocaine reward by suppressing intra-striatal GABA to enhance striatal output. Surprisingly, a mu-opioid receptor antagonist does not block cocaine preference in mice with low striatal D2Rs, implicating other opioid receptors. The bidirectional regulation of enkephalin by D2R activity and cocaine offers insights into mechanisms underlying the vulnerability for cocaine abuse.

Indexed as

CocaineCocaine-Related DisordersAnalgesics, OpioidAnimalsCorpus StriatumEnkephalin, MethionineEnkephalinsgamma-Aminobutyric AcidMiceNarcotic AntagonistsReceptors, Dopamine D1Receptors, Dopamine D2RewardRNA, MessengerAnalgesics, OpioidCocaineEnkephalin, MethionineEnkephalinsgamma-Aminobutyric AcidNarcotic AntagonistsReceptors, Dopamine D1Receptors, Dopamine D2RNA, MessengeraddictioncocaineCP: NeuroscienceD2-receptordopamineenkephalinGABArewardstriatumsynapticwithdrawal

Identifiers

PMID36170833
PMCPMC9620395
OpenAlexW4297373822

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.