ArticleBiological psychiatry2014
Methamphetamine downregulates striatal glutamate receptors via diverse epigenetic mechanisms.
Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Role of microRNAs in the pathophysiology of addiction.Wiley interdisciplinary reviews. RNA · 2021Pooled it
- Effects of chronic methamphetamine exposure on rewarding behavior and neurodegeneration markers in adult mice.Psychopharmacology · 2023Trial
- Epigenetic markers as predictors of neurotoxicity and abuse potential of psychotropic drugs: integration of epigenetic modifications in New Approach Methodologies.Archives of toxicology · 2026Review
- Subthreshold Thermal Stress Aggravates Methamphetamine-Induced Cardiomyocyte Pyroptosis via the Mitochondrial ROS/BAX/mtDNA/NLRP3 Pathway.International journal of molecular sciences · 2026Article
- Protective effects of vitamin E and quercetin against MDMA-induced cardiac and hematological dysfunction in male wistar rats.Pflugers Archiv : European journal of physiology · 2026Article
- A single extinction-based treatment with N-Acetylcysteine produces long-term reduction in cocaine relapse.Translational psychiatry · 2026Article
- Addictive drug abuse and depression-a focus on epigenetics.Communications biology · 2026Review
- Prolonged visual experience accelerates developmental synaptic downscaling via epigenetic regulation and Rab5c mediated AMPA receptor trafficking.Communications biology · 2026Article
- Epigenetic Landscapes of Methamphetamine Addiction: Unravelling the Diagnostic Potential of Gene Methylation.Addiction biology · 2025Article
- Article
- Decoding Encoded Cravings: Epigenetic Drivers of Addiction.Brain sciences · 2025Review
- Epigenetic and Genotoxic Mechanisms of PFAS-Induced Neurotoxicity: A Molecular and Transgenerational Perspective.Toxics · 2025Review
- The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder.Biomolecules · 2025Article
- Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025Review
- Research progress of DNA methylation on the regulation of substance use disorders and the mechanisms.Frontiers in cellular neuroscience · 2025Review
- Inhibition of RtTg neurons reverses methamphetamine-induced attention deficits.Acta neuropathologica communications · 2024Article
- Genetic Polymorphisms of Prokineticins and Prokineticin Receptors Associated with Human Disease.Life (Basel, Switzerland) · 2024Review
- An update: epigenetic mechanisms underlying methamphetamine addiction.Frontiers in cell and developmental biology · 2024Review
- The Common Denominators of Parkinson's Disease Pathogenesis and Methamphetamine Abuse.Current neuropharmacology · 2024Review
- ACSS2-dependent histone acetylation improves cognition in mouse model of Alzheimer's disease.Molecular neurodegeneration · 2023Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic methamphetamine (METH) exposure causes neuroadaptations at glutamatergic synapses.
methodsTo identify the METH-induced epigenetic underpinnings of these neuroadaptations, we injected increasing METH doses to rats for 2 weeks and measured striatal glutamate receptor expression. We then quantified the effects of METH exposure on histone acetylation. We also measured METH-induced changes in DNA methylation and DNA hydroxymethylation.
resultsChronic METH decreased transcript and protein expression of GluA1 and GluA2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) and GluN1 N-methyl-D-aspartate receptor subunits. These changes were associated with altered electrophysiological glutamatergic responses in striatal neurons. Chromatin immunoprecipitation-polymerase chain reaction revealed that METH decreased enrichment of acetylated histone H4 on GluA1, GluA2, and GluN1 promoters. Methamphetamine exposure also increased repressor element-1 silencing transcription factor (REST) corepressor 1, methylated CpG binding protein 2, and histone deacetylase 2 enrichment, but not of sirtuin 1 or sirtuin 2, onto GluA1 and GluA2 gene sequences. Moreover, METH caused interactions of REST corepressor 1 and methylated CpG binding protein 2 with histone deacetylase 2 and of REST with histone deacetylase 1. Surprisingly, methylated DNA immunoprecipitation and hydroxymethylated DNA immunoprecipitation-polymerase chain reaction revealed METH-induced decreased enrichment of 5-methylcytosine and 5-hydroxymethylcytosine at GluA1 and GluA2 promoter sequences. Importantly, the histone deacetylase inhibitor, valproic acid, blocked METH-induced decreased expression of AMPAR and N-methyl-D-aspartate receptor subunits. Finally, valproic acid also attenuated METH-induced decrease H4K16Ac recruitment on AMPAR gene sequences.
conclusionsThese observations suggest that histone H4 hypoacetylation may be the main determinant of METH-induced decreased striatal glutamate receptor expression.
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