Evidence map›Paper›PMID 26879809›Full record

ArticleNature communications2016

Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain.

Zachary Freyberg, Mark S Sonders, Jenny I Aguilar, Takato Hiranita, Caline S Karam, Jorge Flores, Andrea B Pizzo, Yuchao Zhang, Zachary J Farino, Audrey Chen and 15 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

78 citing papers in PubMed, 128 citations in OpenAlex.

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18 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

25 authors at 8 institutions in 2 countries.

Zachary FreybergDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Mark S SondersDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Jenny I AguilarDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Takato HiranitaPsychobiology Section, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
Caline S KaramDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Jorge FloresDepartment of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Andrea B PizzoDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Yuchao ZhangDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Zachary J FarinoDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Audrey ChenDepartment of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, David Geffen School of Medicine University of California, Los Angeles, California 90095, USA.
Ciara A MartinUCLA Interdepartmental Program in Molecular Toxicology, University of California, Los Angeles, California 90095, USA.
Theresa A KopajticPsychobiology Section, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
Hao FeiDepartment of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, David Geffen School of Medicine University of California, Los Angeles, California 90095, USA.
Gang HuDepartment of Chemistry, Columbia University, New York, New York 10027, USA.
Yi-Ying LinSchool of Pharmacy, College of Medicine, National Taiwan University, Taipei, Republic of China 10055.
Eugene V MosharovDepartment of Neurology, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Brian D McCabeCenter for Motor Neuron Biology and Disease, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Robin FreybergDepartment of Psychology, Stern College for Women, Yeshiva University, New York, New York 10016, USA.
Kandatege WimalasenaDepartment of Chemistry, Wichita State University, Wichita, Kansas 67260, USA.
Ling-Wei HsinSchool of Pharmacy, College of Medicine, National Taiwan University, Taipei, Republic of China 10055.
Dalibor SamesDepartment of Chemistry, Columbia University, New York, New York 10027, USA.
David E KrantzDepartment of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, David Geffen School of Medicine University of California, Los Angeles, California 90095, USA.
Jonathan L KatzPsychobiology Section, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
David SulzerDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
Jonathan A JavitchDepartment of Psychiatry, College of Physicians &Surgeons, Columbia University, New York, New York 10032, USA.
New York Psychoanalytic Society and Institute · USColumbia University · USUniversity of California, Los Angeles · USNational Institute on Drug Abuse · USNational Taiwan University · TWHoward Hughes Medical Institute · USWichita State University · USYeshiva University · US

Funding

Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
The Presynaptic Vesicle Cycle for the Slow Acting Neurotransmitter SecretionP01DA010154 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KREITZER, ANATOL, KREITZER, ANATOL · 1995 to 2016
$14.7M
STRUCTURE/FUNCTION OF THE HUMAN DOPAMINE TRANSPORTERP01DA012408 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI WEINSTEIN, HAREL · 1999 to 2015
$14.2M
TRAINING IN PHARMACOLOGICAL SCIENCEST32GM007628 · NIGMS · VANDERBILT UNIVERSITY · PI BARNETT, JOEY VICTOR, KAVALALI, EGE T · 1985 to 2022
$11.2M
The Dopamine Synapse and Associative LearningR01DA007418 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI David Sulzer · 1999 to 2026
$9.4M
Project 4: Pesticides and Genes In PD: Studies In HumansP01ES016732 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHESSELET, MARIE-FRANCOISE S · 2008 to 2012
$6.7M
Development of Fluorescent False NeurotransmittersR01MH108186 · NIMH · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SAMES, DALIBOR, SULZER, DAVID · 2015 to 2024
$5.8M
Basic Dopamine Transporter Mechanisms Of CocaineZIADA000103 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI KATZ, JONATHAN L · 2009 to 2016
$4.6M
Training in Molecular ToxicologyT32ES015457 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ALLARD, PATRICK, HANKINSON, OLIVER NMN · 2008 to 2025
$4.0M
Environmental toxin interactions with genetic risks for Parkinson's diseaseR01ES015747 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KRANTZ, DAVID EVAN · 2007 to 2011
$2.1M
The Influence of Neurotransmitter Transport on Aminergic NeuromodulationR01MH107390 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KRANTZ, DAVID EVAN · 2015 to 2019
$1.9M
Howard Hughes Medical InstituteIntramural NIH HHSNIA NIH HHS AG08702NIA NIH HHS P50 AG008702NIDA NIH HHS K05 DA022413NIDA NIH HHS K08 DA031241NIDA NIH HHS P01 DA0 10154NIDA NIH HHS P01 DA010154NIDA NIH HHS P01 DA012408NIDA NIH HHS P01 DA12408NIDA NIH HHS R01 DA007418NIEHS NIH HHS P01 ES016732NIEHS NIH HHS R01 ES015747NIEHS NIH HHS T32 ES015457NIGMS NIH HHS GM07185NIGMS NIH HHS T32 GM007185NIGMS NIH HHS T32 GM007628NIMH NIH HHS R01 MH076900NIMH NIH HHS R01 MH086545NIMH NIH HHS R01 MH107390NIMH NIH HHS R01 MH108186NINDS NIH HHS NS075572NINDS NIH HHS R01 NS075222NINDS NIH HHS R21 NS075572
6 · The paper itself

Abstract

Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H(+) antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects.

Indexed as

AmphetamineAnimalsAnimals, Genetically ModifiedBrainCocaineDopamineDopamine AgentsDopamine Plasma Membrane Transport ProteinsDopaminergic NeuronsDrosophila melanogasterHEK293 CellsHumansImage Processing, Computer-AssistedLocomotionMethamphetamineMethylphenidateAmphetamineCocaineDopamineDopamine AgentsDopamine Plasma Membrane Transport ProteinsMethamphetamineMethylphenidateSlc18a2 protein, ratVesicular Monoamine Transport Proteins

Identifiers

PMID26879809
PMCPMC4757768
OpenAlexW2304380155

What OpenQuestion holds

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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.