Evidence map›Paper›PMID 24853388›Full record

ArticleBiological psychiatry2014

Preference for distinct functional conformations of the dopamine transporter alters the relationship between subjective effects of cocaine and stimulation of mesolimbic dopamine.

Stephen J Kohut, Takato Hiranita, Soo-Kyung Hong, Aaron L Ebbs, Valeria Tronci, Jennifer Green, Linda Garcés-Ramírez, Lauren E Chun, Maddalena Mereu, Amy H Newman and 2 more

Abstract read
In one paragraph

Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

38 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Potential therapeutics for effort-related motivational dysfunction: assessing novel atypical dopamine transport inhibitors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  5. Article
  6. Article
  7. Modafinil, an atypical CNS stimulant?Advances in pharmacology (San Diego, Calif.) · 2024
    Article
  8. Article
  9. Article
  10. Vigor, Effort-Related Aspects of Motivation and Anhedonia.Current topics in behavioral neurosciences · 2022
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Modafinil potentiates cocaine self-administration by a dopamine-independent mechanism: possible involvement of gap junctions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020
    Article
  18. Article
  19. Article
  20. Translating the atypical dopamine uptake inhibitor hypothesis toward therapeutics for treatment of psychostimulant use disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019
    Article
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 2 institutions in 3 countries.

Stephen J KohutPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Takato HiranitaPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Soo-Kyung HongPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Aaron L EbbsPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Valeria TronciPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Jennifer GreenPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Linda Garcés-RamírezPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland; Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, México.
Lauren E ChunPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Maddalena MereuPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Amy H NewmanMedicinal Chemistry Sections, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland; Medications Development Program, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Jonathan L KatzPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland.
Gianluigi TandaPsychobiology, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland; Medications Development Program, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse/Intramural Research Program/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland. Electronic address: gtanda@mail.nih.gov.
National Institutes of Health · USNational Institute on Drug Abuse · US

Funding

Novel Probes for the Monoamine TransportersZIADA000389 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI NEWMAN, AMY HAUCK · 2009 to 2025
$14.4M
Preclinical medication development for stimulant use disorderZIADA000522 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI BAUMANN, MICHAEL · 2009 to 2025
$8.9M
Basic Dopamine Transporter Mechanisms Of CocaineZIADA000103 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI KATZ, JONATHAN L · 2009 to 2016
$4.6M
Intramural NIH HHS ZIA DA000103Intramural NIH HHS ZIA DA000522
6 · The paper itself

Abstract

backgroundSubjective effects of cocaine are mediated primarily by dopamine (DA) transporter (DAT) blockade. The present study assessed the hypothesis that different DAT conformational equilibria regulate differences in cocaine-like subjective effects and extracellular DA induced by diverse DA-uptake inhibitors (DUIs).

methodsThe relationship between cocaine-like subjective effects and stimulation of mesolimbic DA levels by standard DUIs (cocaine, methylphenidate, WIN35,428) and atypical DUIs (benztropine analogs: AHN1-055, AHN2-005, JHW007) was investigated using cocaine discrimination and DA microdialysis procedures in rats.

resultsAll drugs stimulated DA levels with different maxima and time courses. Standard DUIs, which preferentially bind outward-facing DAT conformations, fully substituted for cocaine, consistently producing cocaine-like subjective effects at DA levels of 100-125% over basal values, regardless of dose or pretreatment time. The atypical DUIs, with DAT binding minimally affected by DAT conformation, produced inconsistent cocaine-like subjective effects. Full effects were obtained, if at all, only at a few doses and pretreatment times and at DA levels 600-700% greater than basal values. Importantly, the linear, time-independent, relationship between cocaine-like subjective effects and DA stimulation obtained with standard DUIs was not obtained with the atypical DUIs.

conclusionsThese results suggest a time-related desensitization process underlying the reduced cocaine subjective effects of atypical DUIs that may be differentially induced by the binding modalities identified using molecular approaches. Since the DAT is the target of several drugs for treating neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder, these results help to identify safe and effective medications with minimal cocaine-like subjective effects that contribute to abuse liability.

Indexed as

AnimalsCocaineConditioning, OperantDopamineDopamine Plasma Membrane Transport ProteinsDopamine Uptake InhibitorsMaleMicrodialysisNucleus AccumbensProtein ConformationRatsRats, Sprague-DawleySelf AdministrationCocaineDopamineDopamine Plasma Membrane Transport ProteinsDopamine Uptake InhibitorsADHDbenztropine analogscocaine discriminationdopamine microdialysisdrug abuse and addictionnucleus accumbens shell

Identifiers

PMID24853388
PMCPMC4353924
OpenAlexW2050614558

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.