ArticlePLoS biology2007
Drug-induced epigenetic changes produce drug tolerance.
Article in PLoS biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed, 77 citations in OpenAlex.
- AlteredeNeuro · 2026Article
- SWI/SNF complexes modulate gene expression and the development of physical dependence to ethanol.Alcohol, clinical & experimental research · 2026Article
- AlteredbioRxiv : the preprint server for biology · 2025Article
- A Brief Overview of Ethanol Tolerance and Its Potential Association with Circadian Rhythm inInternational journal of molecular sciences · 2024Review
- Molecular and functional characterization of reversible-sunitinib-tolerance state in human renal cell carcinoma.Journal of cellular and molecular medicine · 2024Article
- Non-coding RNA in alcohol use disorder by affecting synaptic plasticity.Experimental brain research · 2022Review
- Review
- Epigenetic and non-coding regulation of alcohol abuse and addiction.International review of neurobiology · 2021Article
- Flying Together:International journal of molecular sciences · 2020Review
- Genetic Signatures of Drug Response Variability inGenetics · 2019Article
- Article
- Epigenetic Mechanisms of Alcohol Neuroadaptation: Insights fromJournal of experimental neuroscience · 2018Review
- Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats.Frontiers in pharmacology · 2018Article
- Genetics and genomics of alcohol responses in Drosophila.Neuropharmacology · 2017Review
- The role of epigenomics in personalized medicine.Expert review of precision medicine and drug development · 2017Article
- Alcohol-Induced Neuroadaptation Is Orchestrated by the Histone Acetyltransferase CBP.Frontiers in molecular neuroscience · 2017Article
- Sir2/Sirt1 Links Acute Inebriation to Presynaptic Changes and the Development of Alcohol Tolerance, Preference, and Reward.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- A DNA element in the slo gene modulates ethanol tolerance.Alcohol (Fayetteville, N.Y.) · 2016Article
- SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- A histone modification identifies a DNA element controlling slo BK channel gene expression in muscle.Journal of neurogenetics · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Tolerance to drugs that affect neural activity is mediated, in part, by adaptive mechanisms that attempt to restore normal neural excitability. Changes in the expression of ion channel genes are thought to play an important role in these neural adaptations. The slo gene encodes the pore-forming subunit of BK-type Ca(2+)-activated K(+) channels, which regulate many aspects of neural activity. Given that induction of slo gene expression plays an important role in the acquisition of tolerance to sedating drugs, we investigated the molecular mechanism of gene induction. Using chromatin immunoprecipitation followed by real-time PCR, we show that a single brief sedation with the anesthetic benzyl alcohol generates a spatiotemporal pattern of histone H4 acetylation across the slo promoter region. Inducing histone acetylation with a histone deacetylase inhibitor yields a similar pattern of changes in histone acetylation, up-regulates slo expression, and phenocopies tolerance in a slo-dependent manner. The cAMP response element binding protein (CREB) is an important transcription factor mediating experience-based neuroadaptations. The slo promoter region contains putative binding sites for the CREB transcription factor. Chromatin immunoprecipitation assays show that benzyl alcohol sedation enhances CREB binding within the slo promoter region. Furthermore, activation of a CREB dominant-negative transgene blocks benzyl alcohol-induced changes in histone acetylation within the slo promoter region, slo induction, and behavioral tolerance caused by benzyl alcohol sedation. These findings provide unique evidence that links molecular epigenetic histone modifications and transcriptional induction of an ion channel gene with a single behavioral event.
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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.