ArticlePloS one2017
5-Aza-2'-deoxycytidine in the medial prefrontal cortex regulates alcohol-related behavior and Ntf3-TrkC expression in rats.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- The Impact of Alcohol-Induced Epigenetic Modifications in the Treatment of Alcohol use Disorders.Current medicinal chemistry · 2024Review
- DNA Methylation in Alcohol Use Disorder.International journal of molecular sciences · 2023Review
- Is DNA methylation in the brain a mechanism of alcohol use disorder?Frontiers in behavioral neuroscience · 2023Review
- Repeated Ethanol Exposure Alters DNA Methylation Status and Dynorphin/Kappa-Opioid Receptor Expression in Nucleus Accumbens of Alcohol-Preferring AA Rats.Frontiers in genetics · 2021Article
- Alcohol Intoxication and Cognition: Implications on Mechanisms and Therapeutic Strategies.Frontiers in neuroscience · 2020Review
- Role of GABRD Gene Methylation in the Nucleus Accumbens in Heroin-Seeking Behavior in Rats.Frontiers in pharmacology · 2020Article
- Nucleus accumbens shell small conductance potassium channels underlie adolescent ethanol exposure-induced anxiety.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Epigenetic pharmacotherapy for substance use disorder.Biochemical pharmacology · 2019Review
- Transcriptional Regulators as Targets for Alcohol Pharmacotherapies.Handbook of experimental pharmacologyArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have indicated that DNA methylation plays an important role in the development of alcohol abuse. 5-Aza-2'-deoxycytidine (5-Aza-dc), an inhibitor of DNA methyltransferases, was FDA approved for myelodysplastic syndrome treatment. However, it is unclear whether 5-Aza-dc is involved in alcohol abuse. In this study, using a chronic alcohol exposure model in rats, 5-Aza-dc was injected into the medial prefrontal cortex (mPFC). Alcohol-drinking behavior and the anxiety related behavior were evaluated by two-bottle choice and open field test. We found that 5-Aza-dc injection into the mPFC significantly decreased alcohol consumption and alcohol preference in alcohol-exposure rats, corresponding to the reduced blood alcohol levels. Although 5-Aza-dc potentiated the anxiety-like behavior of alcohol-exposure rats, it had no effect on the locomotor activity. Moreover, both of the mRNA and protein levels of DNA Methyltransferase 3A (DNMT3A) and DNMT3B in the mPFC were upregulated after 35 days of alcohol exposure and this upregulation could be reversed by 5-Aza-dc treatment. Additionally, 5-Aza-dc reversed the alcohol-induced downregulation of neurotrophin-3 (Ntf3), correspondingly the expression of its receptor-TrkC was reduced. These findings identified a functional role of 5-Aza-dc in alcohol-related behavioral phenotypes and one of the potential target genes, Ntf3. We also provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcohol abuse.
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