ArticleScience advances2017
Prior alcohol use enhances vulnerability to compulsive cocaine self-administration by promoting degradation of HDAC4 and HDAC5.
Article in Science advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- E2F3a transcription factor mediates behavioral, cellular, and DNA-protein regulation of cocaine reward in the nucleus accumbens.Molecular psychiatry · 2026Article
- Fentanyl Induces Behavioral Sensitization and Decreases Class IIa HDAC Expression-Activity in Brain as Measured by [Brain sciences · 2026Article
- Regulation of Chromatin Acetylation by Alcohol: Dependence on Sex, Brain Region, and Mode of Exposure.Genes · 2026Review
- Epigenetic Control of an Auxiliary Subunit of Voltage-Gated Sodium Channels Regulates the Strength of Drug-Cue Associations and Relapse-Like Cocaine Seeking.Biological psychiatry · 2025Article
- Class IIa HDACs Are Important Signal Transducers with Unclear Enzymatic Activities.Biomolecules · 2025Review
- Animal models of cocaine use: importance of social context and co-use.Trends in pharmacological sciences · 2025Review
- Epigenetic Dysregulation in Alcohol-Associated Behaviors: Preclinical and Clinical Evidence.Current topics in behavioral neurosciences · 2025Review
- Social hierarchy modulates drug reinforcement and protein phosphorylation in the nucleus accumbens.Frontiers in pharmacology · 2025Article
- Design and radiosynthesis of class-IIa HDAC inhibitor with high molar activity via repositioning theScientific reports · 2024Article
- Plasma Lysophosphatidic Acid Concentrations in Sex Differences and Psychiatric Comorbidity in Patients with Cocaine Use Disorder.International journal of molecular sciences · 2023Article
- Histone Deacetylase 4 Inhibition Reduces Rotenone-Induced Alpha-Synuclein Accumulation via Autophagy in SH-SY5Y Cells.Brain sciences · 2023Article
- Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- An orbitofrontal cortex-anterior insular cortex circuit gates compulsive cocaine use.Science advances · 2022Article
- 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
- Epigenetic Effects of Addictive Drugs in the Nucleus Accumbens.Frontiers in molecular neuroscience · 2022Review
- Sex-specific transcriptional rewiring in the brain of Alzheimer's disease patients.Frontiers in aging neuroscience · 2022Article
- Influence of gender and education on cocaine users in an outpatient cohort in Spain.Scientific reports · 2021Article
- Differential Effects of Histone Deacetylases on the Expression of NKG2D Ligands and NK Cell-Mediated Anticancer Immunity in Lung Cancer Cells.Molecules (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Addiction to cocaine is commonly preceded by experiences with legal or decriminalized drugs, such as alcohol, nicotine, and marijuana. The biological mechanisms by which these gateway drugs contribute to cocaine addiction are only beginning to be understood. We report that in the rat, prior alcohol consumption results in enhanced addiction-like behavior to cocaine, including continued cocaine use despite aversive consequences. Conversely, prior cocaine use has no effect on alcohol preference. Long-term, but not short-term, alcohol consumption promotes proteasome-mediated degradation of the nuclear histone deacetylases HDAC4 and HDAC5 in the nucleus accumbens, a brain region critical for reward-based memory. Decreased nuclear HDAC activity results in global H3 acetylation, creating a permissive environment for cocaine-induced gene expression. We also find that selective degradation of HDAC4 and HDAC5, facilitated by the class II-specific HDAC inhibitor MC1568, enhances compulsive cocaine self-administration. These results parallel our previously reported findings that the gateway drug nicotine enhances the behavioral effects of cocaine via HDAC inhibition. Together, our findings suggest a shared mechanism of action for the gateway drugs alcohol and nicotine, and reveal a novel mechanism by which environmental factors may alter the epigenetic landscape of the reward system to increase vulnerability to cocaine addiction.
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