Evidence map›Paper›PMID 42598825›Full record

ArticleAlcohol, clinical & experimental research2026

Pharmacological Inhibition of HDAC6 Transiently Reduces Voluntary Ethanol Consumption in Male Mice.

Kiera Fleck, Jeffery L Dunning, Max Kreifeldt, Catherine Lopez, Seokjun Jo, Edward Roberts, Candice Contet

Abstract read
In one paragraph

Article in Alcohol, clinical & experimental research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Kiera FleckDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, California, USA.ORCID https://orcid.org/0000-0002-9572-8314
Jeffery L DunningDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, California, USA.ORCID https://orcid.org/0000-0003-0397-4006
Max KreifeldtDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, California, USA.
Catherine LopezDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, California, USA.ORCID https://orcid.org/0009-0005-4693-7012
Seokjun JoDepartment of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
Edward RobertsDepartment of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
Candice ContetDepartment of Translational Medicine, The Scripps Research Institute, La Jolla, California, USA.ORCID https://orcid.org/0000-0002-4459-9540

Funding

Viral Vector CoreP60AA006420 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ERIC P ZORRILLA · 2003 to 2026
$46.3M
Neurpsychopharmacology-Multidisciplinary TrainingT32AA007456 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI MARISA ROBERTO · 1985 to 2026
$13.4M
SYSTEMIC NEUROPHARMACOLOGYP50AA006420 · NIAAA · SCRIPPS RESEARCH INSTITUTE · PI KOOB, GEORGE F · 1985 to 2002
$5.1M
Adaptations to chronic activation of BK channels by ethanol: Contribution to dependence and toleranceR33AA027636 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI CONTET, CANDICE · 2022 to 2024
$1.6M
Role of BK channels in alcohol-induced dysmyelinationR01AA032709 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI Candice Contet · 2025 to 2026
$1.3M
Addiction Training in Discovery, Computation, and Translation to MedicineT32DA062586 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI ERIC P ZORRILLA · 2025 to 2026
$581k
Adaptations to chronic activation of BK channels by ethanol: Contribution to dependence and toleranceR21AA027636 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI CONTET, CANDICE · 2020 to 2021
$473k
NIAAA NIH HHS AA006420NIAAA NIH HHS AA007456NIAAA NIH HHS AA027636NIAAA NIH HHS AA032709NIAAA NIH HHS P50 AA006420NIAAA NIH HHS P60 AA006420NIAAA NIH HHS R01 AA032709NIAAA NIH HHS R21 AA027636NIAAA NIH HHS R33 AA027636NIAAA NIH HHS T32 AA007456NIDA NIH HHS DA062586NIDA NIH HHS T32 DA062586
6 · The paper itself

Abstract

backgroundHistone deacetylase 6 (HDAC6) inhibition can alleviate depression- and anxiety-like behaviors. Accordingly, HDAC6 may be a promising target to mitigate negative reinforcement in alcohol use disorder (AUD). We previously reported reduced α-tubulin acetylation in mice withdrawn from chronic intermittent ethanol (CIE) vapor inhalation, suggesting potential HDAC6 hyperactivity in this mouse model of AUD. The present study aimed to probe the behavioral significance of this acetylation deficit by testing whether HDAC6 inhibition can reverse ethanol drinking escalation in CIE-exposed mice.

methodsMale C57BL/6J mice were subjected to limited-access ethanol drinking sessions (two-bottle choice, 2BC) combined with CIE to escalate voluntary ethanol intake relative to air-exposed counterparts (Air). Ethanol and saccharin intake during 2BC was measured after acute and subchronic administration of bavarostat, a brain-penetrant HDAC6 inhibitor. Acetyl-lysine and acetyl-α-tubulin levels were quantified via immunoblotting.

resultsAcute administration of bavarostat at 100 mg/kg, but not lower doses, significantly reduced ethanol intake in both Air and CIE mice. Ethanol intake during subchronic administration of 100 mg/kg bavarostat was reduced on the first day in both Air and CIE mice compared to vehicle-treated counterparts, but this effect was lost on subsequent days. CIE mice also consumed more saccharin than Air controls. Bavarostat did not impact saccharin intake in either group. When saccharin was offered along with ethanol, CIE mice consumed significantly more ethanol and less saccharin than Air counterparts, indicating intact taste discrimination. Bavarostat administered prior to brain collection significantly increased acetyl-lysine and acetyl-α-tubulin levels in the frontal cortex, confirming reduced HDAC6 activity. These levels did not differ between Air and CIE mice.

conclusionsSystemic administration of bavarostat reduces voluntary ethanol drinking in mice. This effect is dose-dependent, selective for ethanol, independent of ethanol dependence, and transient. These findings support HDAC6 as a viable target to acutely reduce the drive to consume ethanol.

Indexed as

Alcohol DrinkingHistone Deacetylase 6Histone Deacetylase InhibitorsHydroxamic AcidsAcetylationAnimalsEthanolMaleMiceMice, Inbred C57BLTubulinEthanolHdac6 protein, mouseHistone Deacetylase 6Histone Deacetylase InhibitorsHydroxamic AcidsTubulinacetylationalcohol use disorderbavarostatHDAC6α‐tubulin

Identifiers

PMID42598825
PMCPMC13474289

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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.