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

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

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 OUDrelevant 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.

Original languageEnglish
Article numbereadg8558
JournalScience advances
Volume9
Issue number23
DOIs
StatePublished - Jun 2023

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