ArticleFrontiers in pharmacology2020
Role of GABRD Gene Methylation in the Nucleus Accumbens in Heroin-Seeking Behavior in Rats.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Baicalein Alleviates Lithium-Pilocarpine-Induced Status Epilepticus by Regulating DNMT1/GABRD Pathway in Rats.Organogenesis · 2025Article
- Decoding Encoded Cravings: Epigenetic Drivers of Addiction.Brain sciences · 2025Review
- Increased PLAGL1 Gene Methylation in Cord Blood is Positively Correlated with Brain Injury in Chorioamniotic Preterm Infants.Biochemical genetics · 2025Article
- Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025Review
- Substance-Induced Psychiatric Disorders, Epigenetic and Microbiome Alterations, and Potential for Therapeutic Interventions.Brain sciences · 2024Review
- How life events may confer vulnerability to addiction: the role of epigenetics.Frontiers in molecular neuroscience · 2024Review
- Hypoxic Preconditioning Modulates BDNF and Its Signaling through DNA Methylation to Promote Learning and Memory in Mice.ACS chemical neuroscience · 2023Article
- Genetic and epigenetic studies of opioid abuse disorder - the potential for future diagnostics.Expert review of molecular diagnostics · 2023Review
- Oxycodone, an opioid like the others?Frontiers in psychiatry · 2023Review
- Differential expression profiling of tRNA-Derived small RNAs and their potential roles in methamphetamine self-administered rats.Frontiers in genetics · 2023Article
- Prognostic and immunological significance of an M1 macrophage-related gene signature in osteosarcoma.Frontiers in immunology · 2023Article
- Splice-Site Variants in the Gene Encoding GABA-A Receptor Delta Subunit Are Associated with Amphetamine Use in Patients under Methadone Maintenance Treatment.International journal of molecular sciences · 2022Article
- Methylation and expression quantitative trait locus rs6296 in the HTR1B gene is associated with susceptibility to opioid use disorder.Psychopharmacology · 2022Article
- Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma CellsFrontiers in oncology · 2022Article
- Epigenetic Alterations in Prescription Opioid Misuse: New Strategies for Precision Pain Management.Genes · 2021Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic modifications such as DNA methylation play important roles in regulating gene expression and may mediate neuroplasticity and lead to drug-induced aberrant behaviors. Although several brain regions and neurobiological mechanisms have been suggested to be involved in these processes, there is remarkably little known about the effects of DNA methylation on heroin-seeking behavior. Using a Sprague-Dawley rat model, we show that heroin self-administration resulted in gamma-aminobutyric acid type A receptor subunit delta (GABRD) gene hypomethylation, which was associated with transcriptional upregulation of GABRD in the nucleus accumbens (NAc). Systemic l-methionine (MET) administration significantly strengthened the reinstatement of heroin-seeking behavior induced by heroin priming, whereas intra-NAc injections of the DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-Aza-dC) had the opposite effect on heroin-seeking. Meanwhile, 5-Aza-dC treatment decreased DNA methylation and upregulated the expression of GABRD in the NAc, whereas MET had the opposite effect. Our results also reveal that 5-Aza-dC might alter the methylation landscape of the GABRD gene by directly repressing DNMT1 and DNMT3A expression. Furthermore, reinstatement of heroin-seeking behavior was significantly inhibited by directly overexpressing GABRD and remarkably reinforced by GABRD gene silencing in the NAc. Collectively, these results suggest that targeting the GABRD gene and its methylation might represent a novel pharmacological strategy for treating heroin addiction and relapse.
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