ArticleProceedings of the National Academy of Sciences of the United States of America2012
Stress-induced epigenetic regulation of κ-opioid receptor gene involves transcription factor c-Myc.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Kappa opioid receptor availability correlates with depressive symptom burden in chronic migraine: a preliminary investigation.The journal of headache and pain · 2026Article
- G9a inhibition reduces stress-potentiated alcohol drinking in both male and female mice: Implications for safe and effective pharmacological therapeutics for alcohol use disorder.Alcohol, clinical & experimental research · 2026Article
- Multiomic Network Analysis Identifies Dysregulated Neurobiological Pathways in Opioid Addiction.Biological psychiatry · 2025Article
- Article
- Opioid modulation of prefrontal cortex cells and circuits.Neuropharmacology · 2024Review
- Article
- Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury.Nature neuroscience · 2023Article
- Molecular and Epigenetic Aspects of Opioid Receptors in Drug Addiction and Pain Management in Sport.International journal of molecular sciences · 2023Review
- Convergent actions of stress and stimulants via epigenetic regulation of neural circuitry.Trends in neurosciences · 2022Review
- Epigenetic Modulation of Opioid Receptors by Drugs of Abuse.International journal of molecular sciences · 2022Review
- Striatum Hyperactivity Triggers Relapse to Morphine and Methamphetamine (Polydrug) Dependence in Mice.Journal of pharmacy & bioallied sciences · 2020Article
- Turning the 'Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex.Frontiers in behavioral neuroscience · 2020Article
- Buprenorphine prevents stress-induced blunting of nucleus accumbens dopamine response and approach behavior to food reward in mice.Neurobiology of stress · 2019Article
- Targeting opioid dysregulation in depression for the development of novel therapeutics.Pharmacology & therapeutics · 2019Review
- Dual regulation ofThe Journal of cell biology · 2019Article
- Isoproterenol increases histone deacetylase 6 expression and cell migration by inhibiting ERK signaling via PKA and Epac pathways in human lung cancer cells.Experimental & molecular medicine · 2016Article
- The role of the dynorphin/κ opioid receptor system in anxiety.Acta pharmacologica Sinica · 2015Review
- Behavioral stress reduces RIP140 expression in astrocyte and increases brain lipid accumulation.Brain, behavior, and immunity · 2015Article
- Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: etiological contribution to complex regional pain syndromes (Part II).Medical science monitor : international medical journal of experimental and clinical research · 2014Review
- β-arrestin protects neurons by mediating endogenous opioid arrest of inflammatory microglia.Cell death and differentiation · 2014Article
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Authors and funding
4 authors.
Funding
Abstract
Exposure to stress is associated with adverse emotional and behavioral responses. Whereas the κ-opioid receptor (KOR) system is known to mediate some of the effects, it is unclear whether and how stress affects epigenetic regulation of this gene. Because the KOR gene can use two promoters (Pr1 and Pr2) and two polyadenylation signals (PA1 and PA2), it is also interesting whether and how these distinct regulatory mechanisms are differentially modulated by stress. The current study examined the effects of stress on these different regulatory mechanisms of the KOR gene. Results showed that stress selectively increased the expression of KOR mRNA isoforms controlled by Pr1 and terminated at PA1 in specific brain areas including the medial-prefrontal cortex, hippocampus, brainstem, and sensorimotor cortex, but not in the amygdala or hypothalamus. These effects correlated with altered epigenetic state of KOR Pr1 chromatin, as well as elevation and increased recruitment of the principal transcription factor c-Myc, which could activate Pr1. Stress-induced modulation of Pr1 was further validated using glutamate-sensitive murine hippocampal cell line, HT22. The results revealed a common molecular mechanism underlying the effect of stress on selected chromatin regions of this gene at the cellular level and in the context of whole animal and identified a critical role for c-Myc in stress-triggered epigenetic regulation of the KOR gene locus. This study sheds light on the mechanisms of stress-induced epigenetic regulation that targets specific chromatin segments and suggests certain KOR transcripts and its principal transcription factor c-Myc as potential targets for brain-area-specific intervention.
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