Evidence map›Paper›PMID 36543333›Full record

ArticleAlcohol, clinical & experimental research2023

Alcohol withdrawal produces changes in excitability, population discharge probability, and seizure threshold.

Gregory E Alberto, David C Klorig, Allison T Goldstein, Dwayne W Godwin

Open access · hybridAbstract read
In one paragraph

Article in Alcohol, clinical & experimental research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 30% of its field
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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Adolescent Alcohol and the Spectrum of Cognitive Dysfunction in Aging.Advances in experimental medicine and biology · 2025
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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

4 authors at 2 institutions in 1 country.

Gregory E AlbertoDepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, North Carolina, Winston-Salem, USA.
David C KlorigDepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, North Carolina, Winston-Salem, USA.ORCID 0000-0001-8756-771X
Allison T GoldsteinDepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, North Carolina, Winston-Salem, USA.
Dwayne W GodwinDepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, North Carolina, Winston-Salem, USA.ORCID 0000-0002-0376-4968
Wake Forest University · USDartmouth–Hitchcock Medical Center · US

Funding

MULTI-DISCIPLINARY TRAINING IN THE BIOLOGY OF ALCOHOLISMT32AA007565 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI BRIAN A MCCOOL · 1994 to 2026
$10.1M
Mechanisms of Alcohol WithdrawalR01AA016852 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI GODWIN, DWAYNE W · 2008 to 2024
$5.5M
Translational Studies on Early-life Stress and Vulnerability to Alcohol AddictionP01AA021099 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI JONES, SARA RAULERSON · 2012 to 2016
$2.8M
Evaluating Gene Therapy Strategies to Treat Epilepsy Using a Novel Optogenetic Measure of Network Excitability and Seizure SusceptibilityR21NS116519 · NINDS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI GODWIN, DWAYNE W, KLORIG, DAVID C · 2020 to 2021
$434k
An optogenetic investigation of CNS sensitization following alcohol withdrawalF30AA023708 · NIAAA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ALBERTO, GREGORY ERICK · 2014 to 2019
$228k
NIAAA NIH HHS F30 AA023708NIAAA NIH HHS P01 AA021099NIAAA NIH HHS R01 AA016852NIAAA NIH HHS T32 AA007565NINDS NIH HHS R21 NS116519
6 · The paper itself

Abstract

backgroundAlcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death. The development of targeted pharmacotherapies for treating AWS has been slow, due in part to the lack of available animal models that capture the key features of human AWS. Using a unique optogenetic method of probing network excitability, we examined electrophysiologic correlates of hyperexcitability sensitive to early changes in CNS excitability. This method is sensitive to pharmacologic treatments that reduce excitability and may represent a platform for AWS drug development.

methodsWe applied a newly developed method, the optogenetic population discharge threshold (oPDT), which uses light intensity response curves to measure network excitability in chronically implanted mice. Excitability was tracked using the oPDT before, during, and after the chronic intermittent exposure (CIE) model of alcohol withdrawal (WD).

resultsAlcohol withdrawal produced a dose-dependent leftward shift in the oPDT curve (denoting increased excitability), which was detectable in as few as three exposure cycles. This shift in excitability mirrored an increase in the number of spontaneous interictal spikes during withdrawal. In addition, Withdrawal lowered seizure thresholds and increased seizure severity in optogenetically kindled mice.

conclusionWe demonstrate that the oPDT provides a sensitive measure of alcohol withdrawal-induced hyperexcitability. The ability to actively probe the progression of excitability without eliciting potentially confounding seizures promises to be a useful tool in the preclinical development of next-generation pharmacotherapies for AWS.

Indexed as

AlcoholismAlcohol Withdrawal SeizuresSubstance Withdrawal SyndromeAnimalsEthanolHumansMicePatient DischargeSeizuresEthanolalcohol withdrawal syndromeelectrophysiologyinterictal spikesoptogeneticsseizure

Identifiers

PMID36543333
PMCPMC10197957
OpenAlexW4312093666

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.