Evidence map›Paper›PMID 37509143›Full record

ArticleBiomolecules2023

Dopamine Transporter Knockout Rats Display Epigenetic Alterations in Response to Cocaine Exposure.

Samara Vilca, Claes Wahlestedt, Sari Izenwasser, Raul R Gainetdinov, Marta Pardo

Open access · goldAbstract read
In one paragraph

Article in Biomolecules, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. 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

5 authors at 2 institutions in 2 countries.

Samara VilcaDepartment of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Claes WahlestedtDepartment of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Sari IzenwasserDepartment of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Raul R GainetdinovInstitute of Translational Biomedicine, St. Petersburg University Hospital, St. Petersburg State University, Universitetskaya Emb. 7-9, 199034 St. Petersburg, Russia.
Marta PardoDepartment of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
University of Miami · USSt Petersburg University · RU

Funding

Microglia and Epigenetic Regulation in Opioid AddictionDP1DA051828 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TUESTA, LUIS MIGUEL · 2020 to 2024
$2.3M
Epigenetic modulation of amygdalar circuits that control alcohol compulsivityR01AA029924 · NIAAA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Luis Miguel Tuesta, Claes Robert Wahlestedt · 2022 to 2026
$2.1M
BRD4 InhibitorU18DA052533 · NIDA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WAHLESTEDT, CLAES ROBERT · 2020 to 2020
$220k
National Insitute of Health AA029924National Institute of Health DA052533NIAAA NIH HHS R01 AA029924NIDA NIH HHS DP1 DA051828NIDA NIH HHS U18 DA052533
6 · The paper itself

Abstract

(1) Background: There is an urgent need for effective treatments for cocaine use disorder (CUD), and new pharmacological approaches targeting epigenetic mechanisms appear to be promising options for the treatment of this disease. Dopamine Transporter (DAT) transgenic rats recently have been proposed as a new animal model for studying susceptibility to CUD. (2) Methods: DAT transgenic rats were treated chronically with cocaine (10 mg/kg) for 8 days, and the expression of epigenetic modulators, Lysine Demethylase 6B (KDM6B) and Bromodomain-containing protein 4 (BRD4), was examined in the prefrontal cortex (PFC). (3) Results: We show that only full knockout (KO) of DAT impacts basal levels of KDM6B in females. Additionally, cocaine altered the expression of both epigenetic markers in a sex- and genotype-dependent manner. In response to chronic cocaine, KDM6B expression was decreased in male rats with partial DAT mutation (HET), while no changes were observed in wild-type (WT) or KO rats. Indeed, while HET male rats have reduced KDM6B and BRD4 expression, HET female rats showed increased KDM6B and BRD4 expression levels, highlighting the impact of sex on epigenetic mechanisms in response to cocaine. Finally, both male and female KO rats showed increased expression of BRD4, but only KO females exhibited significantly increased KDM6B expression in response to cocaine. Additionally, the magnitude of these effects was bigger in females when compared to males for both epigenetic enzymes. (4) Conclusions: This preliminary study provides additional support that targeting KDM6B and/or BRD4 may potentially be therapeutic in treating addiction-related behaviors in a sex-dependent manner.

Indexed as

CocaineDopamine Plasma Membrane Transport ProteinsAnimalsEpigenesis, GeneticFemaleMaleMiceMice, KnockoutNuclear ProteinsRatsRats, TransgenicTranscription FactorsCocaineDopamine Plasma Membrane Transport ProteinsNuclear ProteinsTranscription FactorsBRD4cocaineDATepigeneticsKDM6Bknockout

Identifiers

PMID37509143
PMCPMC10377455
OpenAlexW4384131417

What OpenQuestion holds

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LicenceCC BY
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.