ArticleProceedings of the National Academy of Sciences of the United States of America2016
Histone arginine methylation in cocaine action in the nucleus accumbens.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Protein Arginine Methyltransferase 6 Regulated Odontogenic Differentiation and Mitochondrial Function of Stem Cells from Apical Papilla Through its Nuclear Localization Sequence via β-catenin Pathway.International dental journal · 2026Article
- Addictive drug abuse and depression-a focus on epigenetics.Communications biology · 2026Review
- PGx-BasedCurrent neuropharmacology · 2026Article
- Why animal models are still needed for discoveries in mental health research.Journal of psychiatry & neuroscience : JPN · 2026Article
- Cocaine and morphine induce shared and divergent transcriptional regulation in nucleus accumbens D1 and D2 medium spiny neurons.Molecular psychiatry · 2025Article
- Protein Arginine Methyltransferases from Regulatory Function to Clinical Implication in Central Nervous System.Cellular and molecular neurobiology · 2025Review
- Cell-type specific epigenetic and transcriptional mechanisms in substance use disorder.Frontiers in cellular neuroscience · 2025Review
- Cell type-specific epigenetic priming of gene expression in nucleus accumbens by cocaine.Science advances · 2024Article
- Review
- Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.Gene & protein in disease · 2024Article
- Solving the Global Opioid Crisis: Incorporating Genetic Addiction Risk Assessment with Personalized Dopaminergic Homeostatic Therapy and Awareness Integration Therapy.Journal of addiction psychiatry · 2024Article
- How life events may confer vulnerability to addiction: the role of epigenetics.Frontiers in molecular neuroscience · 2024Review
- The arginine methyltransferase Prmt1 coordinates the germline arginine methylome essential for spermatogonial homeostasis and male fertility.Nucleic acids research · 2023Article
- Critical Roles of Protein Arginine Methylation in the Central Nervous System.Molecular neurobiology · 2023Review
- Review
- Neuropathic pain as a trigger for histone modifications in limbic circuitry.Genes, brain, and behavior · 2023Article
- Epigenetic Modulation of Opioid Receptors by Drugs of Abuse.International journal of molecular sciences · 2022Review
- Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2022Review
- Dopaminylation in Psychostimulant Use Disorder Protects Against Psychostimulant Seeking Behavior by Normalizing Nucleus Accumbens (NAc) Dopamine Expression.Current psychopharmacology · 2022Article
- PRMT6 physically associates with nuclear factor Y to regulate photoperiodic flowering inaBIOTECH · 2021Article
Corrections and comments
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Authors and funding
26 authors at 8 institutions in 4 countries.
Funding
Abstract
Repeated cocaine exposure regulates transcriptional regulation within the nucleus accumbens (NAc), and epigenetic mechanisms-such as histone acetylation and methylation on Lys residues-have been linked to these lasting actions of cocaine. In contrast to Lys methylation, the role of histone Arg (R) methylation remains underexplored in addiction models. Here we show that protein-R-methyltransferase-6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated cocaine exposure, including self-administration, and in the NAc of cocaine-addicted humans. Such PRMT6 down-regulation occurs selectively in NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2-MSNs), with opposite regulation occurring in D1-MSNs, and serves to protect against cocaine-induced addictive-like behavioral abnormalities. Using ChIP-seq, we identified Src kinase signaling inhibitor 1 (Srcin1; also referred to as p140Cap) as a key gene target for reduced H3R2me2a binding, and found that consequent Srcin1 induction in the NAc decreases Src signaling, cocaine reward, and the motivation to self-administer cocaine. Taken together, these findings suggest that suppression of Src signaling in NAc D2-MSNs, via PRMT6 and H3R2me2a down-regulation, functions as a homeostatic brake to restrain cocaine action, and provide novel candidates for the development of treatments for cocaine addiction.
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Registered trials
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.