Evidence map›Paper›PMID 25107591›Full record

ArticleNeuropharmacology2014

Salvinorin A regulates dopamine transporter function via a kappa opioid receptor and ERK1/2-dependent mechanism.

Bronwyn Kivell, Zeljko Uzelac, Santhanalakshmi Sundaramurthy, Jeyaganesh Rajamanickam, Amy Ewald, Vladimir Chefer, Vanaja Jaligam, Elizabeth Bolan, Bridget Simonson, Balasubramaniam Annamalai and 8 more

Open access · greenAbstract read
In one paragraph

Article in Neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

63 citing papers in PubMed, 103 citations in OpenAlex.

  1. Article
  2. Kappa opioid receptor control of motivated behavior revisited.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  3. Article
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  17. Article
  18. Opioid receptors signaling network.Journal of cell communication and signaling · 2022
    Article
  19. Review
  20. Review

3 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

18 authors at 7 institutions in 2 countries.

Bronwyn KivellSchool of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand; Integrative Neuroscience Section, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
Zeljko UzelacMedical University Vienna, Center for Physiology and Pharmacology, Institute of Pharmacology, Waehringerstrasse 13a, A-1090 Vienna, Austria.
Santhanalakshmi SundaramurthyDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Jeyaganesh RajamanickamDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Amy EwaldSchool of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Vladimir CheferIntegrative Neuroscience Section, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
Vanaja JaligamIntegrative Neuroscience Section, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
Elizabeth BolanIntegrative Neuroscience Section, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
Bridget SimonsonSchool of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Balasubramaniam AnnamalaiDepartment of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Padmanabhan MannangattiDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Thomas E PrisinzanoDepartment of Medicinal Chemistry, University of Kansas, Lawrence, KS 66045, USA.
Ivone GomesDepartment of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Lakshmi A DeviDepartment of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Lankupalle D JayanthiDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Harald H SitteMedical University Vienna, Center for Physiology and Pharmacology, Institute of Pharmacology, Waehringerstrasse 13a, A-1090 Vienna, Austria.
Sammanda RamamoorthyDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: sramamoorthy@vcu.edu.
Toni S ShippenbergIntegrative Neuroscience Section, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
Virginia Commonwealth University · USNational Institute on Drug Abuse · USVictoria University of Wellington · NZIcahn School of Medicine at Mount Sinai · USMedical University of South Carolina · USNational Institutes of Health · USUniversity of Kansas · US

Funding

System Biology Center in New YorkP50GM071558 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SOBIE, ERIC A · 2007 to 2017
$22.8M
Regulation Of Opioid Receptor Signaling by Endogenous PeptidesR01DA008863 · NIDA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Lakshmi A Devi, Elyssa Margolis · 1995 to 2026
$6.1M
Investigation of Neoclerodanes as Novel Opioid LigandsR01DA018151 · NIDA · UNIVERSITY OF KENTUCKY · PI PRISINZANO, THOMAS EDWARD · 2005 to 2020
$5.7M
Post-translational Regulation of Opioid and Cannabinoid Receptors.R37DA008863 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DEVI, LAKSHMI A · 2012 to 2021
$4.6M
Kappa-Opioid Receptor Mediated Regulation of Dopamine TransportR01MH083928 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI RAMAMOORTHY, SAMMANDA · 2010 to 2014
$1.7M
POST-TRANSLATIONAL REGULATION OF OPIOID RECEPTORSK05DA019521 · NIDA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI DEVI, LAKSHMI A · 2005 to 2014
$1.2M
Genetic Models of Serotonin Transporter Regulation Linked to Mental DisordersR21MH091633 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI RAMAMOORTHY, SAMMANDA · 2010 to 2011
$403k
Post-translational regulation of opioid receptorsR56DA008863 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DEVI, LAKSHMI A · 2007 to 2007
$381k
NIDA NIH HHS DA018151NIDA NIH HHS DA019521NIDA NIH HHS DA08863NIDA NIH HHS K05 DA019521NIDA NIH HHS R01 DA008863NIDA NIH HHS R01 DA018151NIDA NIH HHS R37 DA008863NIDA NIH HHS R56 DA008863NIGMS NIH HHS GM071558NIGMS NIH HHS P50 GM071558NIMH NIH HHS MH083928NIMH NIH HHS MH091633NIMH NIH HHS R01 MH083928NIMH NIH HHS R21 MH091633
6 · The paper itself

Abstract

Salvinorin A (SalA), a selective κ-opioid receptor (KOR) agonist, produces dysphoria and pro-depressant like effects. These actions have been attributed to inhibition of striatal dopamine release. The dopamine transporter (DAT) regulates dopamine transmission via uptake of released neurotransmitter. KORs are apposed to DAT in dopamine nerve terminals suggesting an additional target by which SalA modulates dopamine transmission. SalA produced a concentration-dependent, nor-binaltorphimine (BNI)- and pertussis toxin-sensitive increase of ASP(+) accumulation in EM4 cells coexpressing myc-KOR and YFP-DAT, using live cell imaging and the fluorescent monoamine transporter substrate, trans 4-(4-(dimethylamino)-styryl)-N-methylpyridinium) (ASP(+)). Other KOR agonists also increased DAT activity that was abolished by BNI pretreatment. While SalA increased DAT activity, SalA treatment decreased serotonin transporter (SERT) activity and had no effect on norepinephrine transporter (NET) activity. In striatum, SalA increased the Vmax for DAT mediated DA transport and DAT surface expression. SalA up-regulation of DAT function is mediated by KOR activation and the KOR-linked extracellular signal regulated kinase-½ (ERK1/2) pathway. Co-immunoprecipitation and BRET studies revealed that DAT and KOR exist in a complex. In live cells, DAT and KOR exhibited robust FRET signals under basal conditions. SalA exposure caused a rapid and significant increase of the FRET signal. This suggests that the formation of KOR and DAT complexes is promoted in response to KOR activation. Together, these data suggest that enhanced DA transport and decreased DA release resulting in decreased dopamine signalling may contribute to the dysphoric and pro-depressant like effects of SalA and other KOR agonists.

Indexed as

Cell MembraneCorpus StriatumDiterpenes, ClerodaneDopamineDopamine AgentsDopamine Plasma Membrane Transport ProteinsHEK293 CellsHumansMAP Kinase Signaling SystemNorepinephrine Plasma Membrane Transport Proteinsp38 Mitogen-Activated Protein KinasesReceptors, Opioid, kappaSerotonin Plasma Membrane Transport ProteinsDiterpenes, ClerodaneDopamineDopamine AgentsDopamine Plasma Membrane Transport ProteinsNorepinephrine Plasma Membrane Transport Proteinsp38 Mitogen-Activated Protein KinasesReceptors, Opioid, kappasalvinorin ASerotonin Plasma Membrane Transport ProteinsSLC6A2 protein, humanSLC6A4 protein, humanDopamine transporterDysphoricKappa opioid receptorPro-depressantSalvinorin ASerotonin transporterTrafficking

Identifiers

PMID25107591
PMCPMC4188751
OpenAlexW2044412002

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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.