ArticleAddiction biology2018
Novel role and regulation of HDAC4 in cocaine-related behaviors.
Article in Addiction biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption.Nature communications · 2021Pooled it
- E2F3a transcription factor mediates behavioral, cellular, and DNA-protein regulation of cocaine reward in the nucleus accumbens.Molecular psychiatry · 2026Article
- Epigenetic Regulation of Inflammation by Dopamine in Primary Human Macrophages.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic regulation of inflammation by dopamine in primary human macrophages.Frontiers in immunology · 2026Article
- The single-cell opioid responses in the context of HIV (SCORCH) consortium.Molecular psychiatry · 2024Article
- Differential Roles of Oxytocin Receptors in the Prefrontal Cortex and Nucleus Accumbens on Cocaine Self-Administration and Reinstatement of Cued Cocaine Seeking in Male Rats.The international journal of neuropsychopharmacology · 2023Article
- Low- and high-cocaine intake affects the spatial and temporal dynamics of class IIa HDAC expression-activity in the nucleus accumbens and hippocampus of male rats as measured by [18F]TFAHA PET/CT neuroimaging.Addiction neuroscience · 2022Article
- Sex Differences in Psychostimulant Abuse: Implications for Estrogen Receptors and Histone Deacetylases.Genes · 2022Review
- Organic anion transporter 1 is an HDAC4-regulated mediator of nociceptive hypersensitivity in mice.Nature communications · 2022Article
- Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2022Review
- HDAC3 Activity within the Nucleus Accumbens Regulates Cocaine-Induced Plasticity and Behavior in a Cell-Type-Specific Manner.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Exposure to drugs of abuse induce effects that persist across generations.International review of neurobiology · 2021Article
- Article
- HDAC superfamily promoters acetylation is differentially regulated by modafinil and methamphetamine in the mouse medial prefrontal cortex.Addiction biology · 2020Article
- Behavioral Alterations in Mice Carrying HomozygousFrontiers in neuroscience · 2020Article
- Histone deacetylase 4 (HDAC4): a new player in anorexia nervosa?Molecular psychiatry · 2019Review
- A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse.Journal of clinical medicine · 2019Review
- Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving.Biological psychiatry · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Epigenetic mechanisms have been proposed to contribute to persistent aspects of addiction-related behaviors. One family of epigenetic molecules that may regulate maladaptive behavioral changes produced by cocaine use are the histone deacetylases (HDACs)-key regulators of chromatin and gene expression. In particular, the class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) respond to changes in neuronal activity by modulating their distribution between the nucleus and cytoplasm-a process controlled in large part by changes in phosphorylation of conserved residues. Cocaine triggers a transient nuclear accumulation of HDAC5 that functions to limit the development of cocaine reward behavior. However, the role and regulation of the close family member, HDAC4, in cocaine behaviors remain largely unknown. In this study, we report that cocaine and cAMP signaling in striatum produced differential phosphorylation and subcellular localization of HDAC4 and HDAC5. Unlike HDAC5, cocaine exposure induced a modest hyperphosphorylation and nuclear export of HDAC4. Genetic deletion of HDAC4 in the nucleus accumbens reduced acute cocaine-produced locomotion, maximum locomotor sensitization and cocaine reward-related behavior. Interestingly, overexpression of an HDAC4 cytoplasm-concentrated mutant (S266E) increased cocaine reward behavior in the cocaine conditioned place preference assay, suggesting that cocaine-induced nuclear export of HDAC4 might function to facilitate the development of cocaine reward behaviors through a role in the cell cytoplasm. Together, our findings suggest that, despite high sequence homology, HDAC4 and HDAC5 are oppositely regulated by cocaine-induced signaling in vivo and have distinct roles in regulating cocaine behaviors.
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Registered trials
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