Evidence map›Paper›PMID 36965548›Full record

ArticleMolecular and cellular neurosciences2023

Distinct subpopulations of D1 medium spiny neurons exhibit unique transcriptional responsiveness to cocaine.

Robert A Phillips, Jennifer J Tuscher, N Dalton Fitzgerald, Ethan Wan, Morgan E Zipperly, Corey G Duke, Lara Ianov, Jeremy J Day

Open access · hybridAbstract read
In one paragraph

Article in Molecular and cellular neurosciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Article
  3. Altered Postnatal Chromatin Development in the Nucleus Accumbens Primes Enduring Stress Sensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
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  19. Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Robert A PhillipsDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jennifer J TuscherDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
N Dalton FitzgeraldDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Ethan WanDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Morgan E ZipperlyDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Corey G DukeDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Lara IanovDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jeremy J DayDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: jjday@uab.edu.
University of Alabama at Birmingham · US

Funding

Role of Gadd45b in Cocaine-driven Epigenetic and Behavioral DynamicsR01DA054714 · NIDA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI JEREMY J DAY · 2022 to 2026
$3.2M
Reelin Signaling and Function in Cocaine ResponseR01DA053743 · NIDA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DAY, JEREMY J · 2021 to 2025
$2.8M
Epigenetic Control of Brain Reward SystemsDP1DA039650 · NIDA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DAY, JEREMY J · 2015 to 2019
$2.3M
Enhancer RNA Regulation of Experience-dependent Neuroepigenetic ProcessesR01MH114990 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DAY, JEREMY J · 2018 to 2022
$2.3M
NIDA NIH HHS DP1 DA039650NIDA NIH HHS R01 DA053743NIDA NIH HHS R01 DA054714NIMH NIH HHS R01 MH114990
6 · The paper itself

Abstract

Drugs of abuse increase extracellular concentrations of dopamine in the nucleus accumbens (NAc), resulting in transcriptional alterations that drive long-lasting cellular and behavioral adaptations. While decades of research have focused on the transcriptional mechanisms by which drugs of abuse influence neuronal physiology and function, few studies have comprehensively defined NAc cell type heterogeneity in transcriptional responses to drugs of abuse. Here, we used single nucleus RNA-seq (snRNA-seq) to characterize the transcriptome of over 39,000 NAc cells from male and female adult Sprague-Dawley rats following acute or repeated cocaine experience. This dataset identified 16 transcriptionally distinct cell populations, including two populations of medium spiny neurons (MSNs) that express the Drd1 dopamine receptor (D1-MSNs). Critically, while both populations expressed classic marker genes of D1-MSNs, only one population exhibited a robust transcriptional response to cocaine. Validation of population-selective transcripts using RNA in situ hybridization revealed distinct spatial compartmentalization of these D1-MSN populations within the NAc. Finally, analysis of published NAc snRNA-seq datasets from non-human primates and humans demonstrated conservation of MSN subtypes across rat and higher order mammals, and further highlighted cell type-specific transcriptional differences across the NAc and broader striatum. These results highlight the utility in using snRNA-seq to characterize both cell type heterogeneity and cell type-specific responses to cocaine and provides a useful resource for cross-species comparisons of NAc cell composition.

Indexed as

CocaineAnimalsFemaleMaleMammalsMedium Spiny NeuronsMiceMice, Inbred C57BLMice, TransgenicNeuronsNucleus AccumbensRatsRats, Sprague-DawleyReceptors, Dopamine D1Receptors, Dopamine D2CocaineReceptors, Dopamine D1Receptors, Dopamine D2CocaineNucleus accumbenssnRNA-seqTranscriptomics

Identifiers

PMID36965548
PMCPMC10898607
OpenAlexW4360602353

What OpenQuestion holds

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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.