GeneSet Information

Tier IV GS408320 • Differential gene expression in heroin_mice_context-induced heroin-seeking following protracted abstinence

DESCRIPTION:

Authors develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following abstinence, and relapse. Bioinformatics analysis of this rich dataset identified numerous patterns of transcriptional regulation, with both region-specific and pan-circuit biological domains affected by heroin. Integration of RNA-seq data. This design enabled investigation of the transcriptomic landscape in multiple conditions that model distinct aspects of the OUD syndrome: first-ever heroin exposure (SH), ongoing/early withdrawal from heroin intake (H24), context-induced heroin-seeking following protracted abstinence (HS), and a combination of drug-induced and context-induced heroin-seeking representative of a relapse-like episode (HH). with OUD-relevant behavioral outcomes uncovered region-specific molecular changes and biological processes that predispose to OUD vulnerability.

LABEL:

Heroin_mice_context-induced heroin-seeking following protracted abstinence

SCORE TYPE:

Binary

DATE ADDED:

2024-03-15

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Caleb J Browne, Rita Futamura, Angélica Minier-Toribio, Emily M Hicks, Aarthi Ramakrishnan, Freddyson J Martínez-Rivera, Molly Estill, Arthur Godino, Eric M Parise, Angélica Torres-Berrío, Ashley M Cunningham, Peter J Hamilton, Deena M Walker, Laura M Huckins, Yasmin L Hurd, Li Shen, Eric J Nestler

TITLE:

Transcriptional signatures of heroin intake and relapse throughout the brain reward circuitry in male mice.

JOURNAL:

Science advances Jun 2023, Vol 9, pp. eadg8558

ABSTRACT:

Opioid use disorder (OUD) looms as one of the most severe medical crises facing society. More effective therapeutics will require a deeper understanding of molecular changes supporting drug-taking and relapse. Here, we develop a brain reward circuit-wide atlas of opioid-induced transcriptional regulation by combining RNA sequencing (RNA-seq) and heroin self-administration in male mice modeling multiple OUD-relevant conditions: acute heroin exposure, chronic heroin intake, context-induced drug-seeking following abstinence, and relapse. Bioinformatics analysis of this rich dataset identified numerous patterns of transcriptional regulation, with both region-specific and pan-circuit biological domains affected by heroin. Integration of RNA-seq data with OUD-relevant behavioral outcomes uncovered region-specific molecular changes and biological processes that predispose to OUD vulnerability. Comparisons with human OUD RNA-seq and genome-wide association study data revealed convergent molecular abnormalities and gene candidates with high therapeutic potential. These studies outline molecular reprogramming underlying OUD and provide a foundational resource for future investigations into mechanisms and treatment strategies. PUBMED: 37294757
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Annotation Information

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Brain (D001921)
RNA (D012313)
Forecasting (D005544)
Outlines (D020489)
Genome (D016678)
Mice (D051379)
Atlases (D020466)
Comprehension (D032882)
Syndrome (D013577)
Genome-Wide Association Study (D055106)
Therapeutics (D013812)
Heroin (D003932)
Reward (D012201)
Association (D001244)
cervical vertebra 1 (MA:0001421)
brain (MA:0000168)
biological regulation (GO:0065007)
proteasome-activating nucleotidase complex (GO:0022623)
Data handling (EDAM_topic:0091)
RNA (EDAM_topic:0099)
Analysis (EDAM_operation:2945)
Sequencing (EDAM_topic:3168)
Microarray data (EDAM_data:2603)
Data (EDAM_data:0006)
RNA-Seq (EDAM_topic:3170)
Molecular biology reference (EDAM_topic:3047)
rna (EDAM_format:1213)
Design (EDAM_operation:2430)
poly(acrylonitrile) polymer (CHEBI:61639)
heroin (CHEBI:27808)
maleate(2-) (CHEBI:30780)
drug (CHEBI:23888)
poly(acrylonitrile) macromolecule (CHEBI:53571)
ribonucleic acid (CHEBI:33697)
Acute (HP:0011009)
Chronic (HP:0011010)
RNA-seq evidence (ECO:0000295)
syndrome (DOID:225)
disease (EFO:0000408)
exposure (EFO:0000487)
treatment (EFO:0000727)
disease recurrence (EFO:0004952)
transcription profiling by high throughput sequencing (EFO:0002770)
genome (EFO:0004420)
RNA-seq assay (MMO:0000659)
vertebral bone 1 (UBERON:0001092)
brain (UBERON:0000955)
male organism (UBERON:0003101)
anatomical projection (UBERON:0004529)
adult cerebral ganglion (UBERON:6110636)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351