Evidence map›Paper›PMID 25746685›Full record

ArticleACS chemical neuroscience2015

Increased Vesicular Monoamine Transporter 2 (VMAT2; Slc18a2) Protects against Methamphetamine Toxicity.

Kelly M Lohr, Kristen A Stout, Amy R Dunn, Minzheng Wang, Ali Salahpour, Thomas S Guillot, Gary W Miller

Abstract read
In one paragraph

Article in ACS chemical neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 10% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Peripheral catecholamine systems: an evolutionary perspective.American journal of physiology. Regulatory, integrative and comparative physiology · 2025
    Review
  4. Review
  5. Article
  6. Tricyclic and tetracyclic antidepressants upregulate VMAT2 activity and rescue disease-causing VMAT2 variants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
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  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
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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

7 authors at 1 institution in 1 country.

Kelly M Lohr
Kristen A Stout
Amy R Dunn
Minzheng Wang
Ali Salahpour⊥Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Thomas S Guillot
Gary W Miller
University of Toronto · CA

Funding

Pilot Project ProgramP30ES019776 · NIEHS · EMORY UNIVERSITY · PI Carmen Joseph Marsit · 2013 to 2026
$22.6M
Graduate and Postdoctoral Training in ToxicologyT32ES012870 · NIEHS · EMORY UNIVERSITY · PI Carmen Joseph Marsit · 2004 to 2026
$9.1M
Udall Parkinson's Disease Center at Emory University: Circuitry to TherapyP50NS071669 · NINDS · EMORY UNIVERSITY · PI WICHMANN, THOMAS · 2010 to 2015
$6.8M
Vesicular Modulation of Dopamine Neuron ToxicityR01ES023839 · NIEHS · EMORY UNIVERSITY · PI MILLER, GARY W · 2015 to 2025
$5.0M
SV2C: a novel target for inhibition of methamphetamine actionF31DA037652 · NIDA · EMORY UNIVERSITY · PI STOUT, KRISTEN · 2014 to 2015
$86k
VMAT2-mediated rescue of Parkinsons disease pathology and behaviorF31NS084739 · NINDS · EMORY UNIVERSITY · PI LOHR, KELLY M · 2013 to 2015
$73k
Canadian Institutes of Health Research 210296NIDA NIH HHS F31 DA037652NIDA NIH HHS F31DA037652NIEHS NIH HHS ES023839NIEHS NIH HHS P30 ES019776NIEHS NIH HHS P30ES019776NIEHS NIH HHS R01 ES023839NIEHS NIH HHS T32 ES012870NIEHS NIH HHS T32ES012870NINDS NIH HHS F31 NS084739NINDS NIH HHS F31NS084739NINDS NIH HHS P50 NS071669NINDS NIH HHS P50NS071669
6 · The paper itself

Abstract

The psychostimulant methamphetamine (METH) is highly addictive and neurotoxic to dopamine terminals. METH toxicity has been suggested to be due to the release and accumulation of dopamine in the cytosol of these terminals. The vesicular monoamine transporter 2 (VMAT2; SLC18A2) is a critical mediator of dopamine handling. Mice overexpressing VMAT2 (VMAT2-HI) have an increased vesicular capacity to store dopamine, thus augmenting striatal dopamine levels and dopamine release in the striatum. Based on the altered compartmentalization of intracellular dopamine in the VMAT2-HI mice, we assessed whether enhanced vesicular function was capable of reducing METH-induced damage to the striatal dopamine system. While wildtype mice show significant losses in striatal levels of the dopamine transporter (65% loss) and tyrosine hydroxylase (46% loss) following a 4 × 10 mg/kg METH dosing regimen, VMAT2-HI mice were protected from this damage. VMAT2-HI mice were also spared from the inflammatory response that follows METH treatment, showing an increase in astroglial markers that was approximately one-third of that of wildtype animals (117% vs 36% increase in GFAP, wildtype vs VMAT2-HI). Further analysis also showed that elevated VMAT2 level does not alter the ability of METH to increase core body temperature, a mechanism integral to the toxicity of the drug. Finally, the VMAT2-HI mice showed no difference from wildtype littermates on both METH-induced conditioned place preference and in METH-induced locomotor activity (1 mg/kg METH). These results demonstrate that elevated VMAT2 protects against METH toxicity without enhancing the rewarding effects of the drug. Since the VMAT2-HI mice are protected from METH despite higher basal dopamine levels, this study suggests that METH toxicity depends more on the proper compartmentalization of synaptic dopamine than on the absolute amount of dopamine in the brain.

Indexed as

AnimalsBlotting, WesternCentral Nervous System StimulantsImmunohistochemistryMaleMethamphetamineMiceMice, Inbred C57BLMice, TransgenicVesicular Monoamine Transport ProteinsCentral Nervous System StimulantsMethamphetamineSlc18a2 protein, mouseVesicular Monoamine Transport ProteinsdopamineinflammationMethamphetamineneurodegenerationvesicleVMAT2

Identifiers

PMID25746685
PMCPMC4489556
OpenAlexW2026052268

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.