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Transcriptional signatures of heroin intake and relapse throughout the brain reward circuitry in male mice.
- Source :
-
Science advances [Sci Adv] 2023 Jun 09; Vol. 9 (23), pp. eadg8558. Date of Electronic Publication: 2023 Jun 09. - Publication Year :
- 2023
-
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.
Details
- Language :
- English
- ISSN :
- 2375-2548
- Volume :
- 9
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Science advances
- Publication Type :
- Academic Journal
- Accession number :
- 37294757
- Full Text :
- https://doi.org/10.1126/sciadv.adg8558