Evidence map›Paper›PMID 40691915›Full record

ArticleNeuropharmacology2025

Selectively counteracting cerebellar adaptations to chronic alcohol exposure reduces acute alcohol withdrawal severity in C57BL6/N mice.

Nadia A McLean, Samantha N Shippell Stiles, Aspen E Harder, Chloe M Erikson, Gloria J Lee, Dominik Schnalzer, Margot Ernst, Marko D Mihovilovic, Giuseppe Giannotti, David J Rossi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

10 authors.

Nadia A McLeanDepartment of Integrative Physiology and Neuroscience, 1815 Ferdinands Lane, Washington State University, Pullman, WA, 99164-7620, USA.
Samantha N Shippell StilesDepartment of Integrative Physiology and Neuroscience, 1815 Ferdinands Lane, Washington State University, Pullman, WA, 99164-7620, USA.
Aspen E HarderDepartment of Integrative Physiology and Neuroscience, 1815 Ferdinands Lane, Washington State University, Pullman, WA, 99164-7620, USA.
Chloe M EriksonDepartment of Integrative Physiology and Neuroscience, 1815 Ferdinands Lane, Washington State University, Pullman, WA, 99164-7620, USA.
Gloria J LeeDepartment of Integrative Physiology and Neuroscience, 1815 Ferdinands Lane, Washington State University, Pullman, WA, 99164-7620, USA.
Dominik SchnalzerInstitute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9/163, 1060, Vienna, Austria.
Margot ErnstMedical University of Vienna, Division of Pathobiology of the Nervous System, Spitalgasse 4, A-1090, Vienna, Austria.
Marko D MihovilovicInstitute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9/163, 1060, Vienna, Austria.
Giuseppe GiannottiDepartment of Integrative Physiology and Neuroscience, 1815 Ferdinands Lane, Washington State University, Pullman, WA, 99164-7620, USA.
David J RossiDepartment of Integrative Physiology and Neuroscience, 1815 Ferdinands Lane, Washington State University, Pullman, WA, 99164-7620, USA. Electronic address: david.rossi@wsu.edu.

Funding

NEUROSTEROID MODULATION OF ETHANOL WITHDRAWAL SEVERITYR01AA012439 · NIAAA · OREGON HEALTH & SCIENCE UNIVERSITY · PI FINN, DEBORAH A., ROSSI, DAVID J · 2000 to 2017
$4.6M
Cerebellar Contributions to Alcohol Use DisordersR01AA026078 · NIAAA · WASHINGTON STATE UNIVERSITY · PI ROSSI, DAVID J · 2017 to 2021
$1.7M
NIAAA NIH HHS R01 AA012439NIAAA NIH HHS R01 AA026078
6 · The paper itself

Abstract

A critical component of Alcohol Use Disorder (AUD) is alcohol (EtOH) withdrawal and consequent aversive withdrawal symptoms that generate negative reinforcement for renewed EtOH consumption to alleviate such symptoms. Here, we simulated human binge EtOH consumption and subsequent acute withdrawal by exposing male and female C57BL6/N mice to EtOH vapor for varying durations (24-72 h). During acute withdrawal, starting 4 h after removal from EtOH vapor, we used patch-clamp recording in cerebellar slices, combined with behavioral analysis of aversive somatic/motor (performance on the accelerating rotorod) and affective/emotional (ultrasonic vocalizations and blood corticosterone) withdrawal symptoms. We found that cerebellar granule cells (GCs) exhibit a homeostatic downregulation of sIPSC frequency that parallels development of motor discoordination and negative emotional affect, all starting at ∼48-72 h of EtOH vapor exposure. Fitting with the negative reinforcement component of the AUD cycle, re-exposure to EtOH during withdrawal reduced somatic and affective withdrawal symptoms. Importantly, selective chemogenetic inhibition of GCs during withdrawal improved motor coordination, likely via actions at the GC axon terminals, and selective pharmacological inhibition of GCs via enhancement of the tonic GABA

Indexed as

Adaptation, PhysiologicalCerebellumEthanolSubstance Withdrawal SyndromeAnimalsCentral Nervous System DepressantsFemaleMaleMiceMice, Inbred C57BLCentral Nervous System DepressantsEthanolAlcoholCerebellumEtOHGABAMotor impairmentNegative affectNeuroadaptationsWithdrawal

Identifiers

PMID40691915
PMCPMC13102386

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.