1. Transcriptional signatures of heroin intake and relapse throughout the brain reward circuitry in male mice.
- Author
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Browne CJ, Futamura R, Minier-Toribio A, Hicks EM, Ramakrishnan A, Martínez-Rivera FJ, Estill M, Godino A, Parise EM, Torres-Berrío A, Cunningham AM, Hamilton PJ, Walker DM, Huckins LM, Hurd YL, Shen L, and Nestler EJ
- Subjects
- Humans, Mice, Male, Animals, Genome-Wide Association Study, Brain, Reward, Recurrence, Heroin adverse effects, Opioid-Related Disorders
- 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.
- Published
- 2023
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