ArticleNeuron2012
Histone deacetylase 5 limits cocaine reward through cAMP-induced nuclear import.
Article in Neuron, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 114 citations in OpenAlex.
- Histone Deacetylase 5 in Prelimbic Prefrontal Cortex Limits Context-Associated Cocaine Seeking.Biological 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
- 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
- Intrinsic Deacetylation Represses Intrinsic Excitation: HDAC5 and Cocaine Substance Use Disorder.Biological psychiatry · 2025Article
- Class IIa HDACs Are Important Signal Transducers with Unclear Enzymatic Activities.Biomolecules · 2025Review
- The single-cell opioid responses in the context of HIV (SCORCH) consortium.Molecular psychiatry · 2024Article
- NPAS4 supports cocaine-conditioned cues in rodents by controlling the cell type-specific activation balance in the nucleus accumbens.Nature communications · 2024Article
- 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
- Article
- 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
- Overexpressing Histone Deacetylase 5 in Rat Dorsal Striatum Alters Reward-Guided Decision-Making and Associated Neural Encoding.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Cocaine induces paradigm-specific changes to the transcriptome within the ventral tegmental area.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Epigenetics of Drug Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- 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
- Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice.Scientific reports · 2021Article
- Regulation of histone deacetylase activities and functions by phosphorylation and its physiological relevance.Cellular and molecular life sciences : CMLS · 2021Review
- The Mechanisms and Boundary Conditions of Drug Memory Reconsolidation.Frontiers in neuroscience · 2021Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Chromatin remodeling by histone deacetylases (HDACs) is a key mechanism regulating behavioral adaptations to cocaine use. We report here that cocaine and cyclic adenosine monophosphate (cAMP) signaling induce the transient nuclear accumulation of HDAC5 in rodent striatum. We show that cAMP-stimulated nuclear import of HDAC5 requires a signaling mechanism that involves transient, protein phosphatase 2A (PP2A)-dependent dephosphorylation of a Cdk5 site (S279) found within the HDAC5 nuclear localization sequence. Dephosphorylation of HDAC5 increases its nuclear accumulation, by accelerating its nuclear import rate and reducing its nuclear export rate. Importantly, we show that dephosphorylation of HDAC5 S279 in the nucleus accumbens suppresses the development, but not expression, of cocaine reward behavior in vivo. Together, our findings reveal a molecular mechanism by which cocaine regulates HDAC5 function to antagonize the rewarding impact of cocaine, likely by putting a brake on drug-stimulated gene expression that supports drug-induced behavioral changes.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.