Evidence map›Paper›PMID 25293837›Full record

ArticleAlcoholism, clinical and experimental research2014

Chronic intermittent ethanol exposure and withdrawal alters (3α,5α)-3-hydroxy-pregnan-20-one immunostaining in cortical and limbic brain regions of C57BL/6J mice.

Antoniette M Maldonado-Devincci, Jason B Cook, Todd K O'Buckley, Danielle H Morrow, Raechel E McKinley, Marcelo F Lopez, Howard C Becker, A Leslie Morrow

Abstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.9field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 32 citations in OpenAlex.

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  12. Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol.Handbook of experimental pharmacology · 2018
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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

8 authors at 3 institutions in 1 country.

Antoniette M Maldonado-DevincciCurriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Jason B Cook
Todd K O'Buckley
Danielle H Morrow
Raechel E McKinley
Marcelo F Lopez
Howard C Becker
A Leslie Morrow
University of North Carolina at Chapel Hill · USMedical University of South Carolina · USUnited States Department of Veterans Affairs · US

Funding

TREATING ETHANOL WITHDRAWAL WITH LORAZEPAM/NALTREXONEP50AA010761 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HOWARD C. BECKER · 1996 to 2026
$46.8M
UNC ARC Information/Dissemination CoreP60AA011605 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash · 2003 to 2026
$46.3M
TOXICOLOGYT32ES007126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ILONA JASPERS, Bernard E. Weissman · 1985 to 2026
$13.0M
Ethanol Dependence &Stress Effects on Ethanol DrinkingU01AA014095 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HOWARD C. BECKER · 2003 to 2026
$9.0M
Mouse Chronic Intermittent Ethanol (CIE) CoreU01AA020929 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI LOPEZ, MARCELO F. · 2012 to 2015
$1.5M
Stress, alcohol and GABAergic neuroactive steroids in primatesU01AA016672 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MORROW, A LESLIE · 2007 to 2011
$1.4M
Neuroactive Steroids and Allostasis Induced by Ethanol/StressU01AA020935 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MORROW, A LESLIE · 2012 to 2016
$1.1M
NIAAA NIH HHS AA010761NIAAA NIH HHS P50 AA010761NIAAA NIH HHS P60 AA011605NIAAA NIH HHS U01 AA014095NIAAA NIH HHS U01-AA014095NIAAA NIH HHS U01 AA016672NIAAA NIH HHS U01-AA016672NIAAA NIH HHS U01 AA020929NIAAA NIH HHS U01-AA020929NIAAA NIH HHS U01 AA020935NIAAA NIH HHS U01-AA020935NIEHS NIH HHS T32 ES007126
6 · The paper itself

Abstract

backgroundThe GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) has been studied during withdrawal from ethanol (EtOH) in humans, rats, and mice. Serum 3α,5α-THP levels decreased, and brain levels were not altered following acute EtOH administration (2 g/kg) in male C57BL/6J mice; however, the effects of chronic intermittent ethanol (CIE) exposure on 3α,5α-THP levels have not been examined. Given that CIE exposure changes subsequent voluntary EtOH drinking in a time-dependent fashion following repeated cycles of EtOH exposure, we conducted a time-course analysis of CIE effects on 3α,5α-THP levels in specific brain regions known to influence drinking behavior.

methodsAdult male C57BL/6J mice were exposed to 4 cycles of CIE to induce EtOH dependence. All mice were sacrificed and perfused at 1 of 2 time points, 8 or 72 hours following the final exposure cycle. Free-floating brain sections (40 μm; 3 to 5 sections/region/animal) were immunostained and analyzed to determine relative levels of cellular 3α,5α-THP.

resultsWithdrawal from CIE exposure produced time-dependent and region-specific effects on immunohistochemical detection of 3α,5α-THP levels across cortical and limbic brain regions. A transient reduction in 3α,5α-THP immunoreactivity was observed in the central nucleus of the amygdala 8 hours after withdrawal from CIE (-31.4 ± 9.3%). Decreases in 3α,5α-THP immunoreactivity were observed 72 hours following withdrawal in the medial prefrontal cortex (-25.0 ± 9.3%), nucleus accumbens core (-29.9 ± 6.6%), and dorsolateral striatum (-18.5 ± 6.0%), while an increase was observed in the CA3 pyramidal cell layer of the hippocampus (+42.8 ± 19.5%). Sustained reductions in 3α,5α-THP immunoreactivity were observed at both time points in the lateral amygdala (8 hours -28.3 ± 12.8%; 72 hours -27.5 ± 12.4%) and in the ventral tegmental area (8 hours -26.5 ± 9.9%; 72 hours -31.6 ± 13.8%).

conclusionsThese data suggest that specific neuroadaptations in 3α,5α-THP levels may be present in regions of brain that mediate anxiety, stress, and reinforcement relevant to EtOH dependence. The changes that occur at different time points likely modulate neurocircuitry involved in EtOH withdrawal as well as the elevated drinking observed after CIE exposure.

Indexed as

Withholding TreatmentAlcoholismAnimalsAnxietyCentral Amygdaloid NucleusCorpus StriatumDose-Response Relationship, DrugEthanolHippocampusMaleMiceMice, Inbred C57BLModels, AnimalNucleus AccumbensPrefrontal CortexPregnanoloneEthanolPregnanolone3α,5α-THPAlcoholAllopregnanoloneNeuroactive SteroidWithdrawal

Identifiers

PMID25293837
PMCPMC4211975
OpenAlexW2017808263

What OpenQuestion holds

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Registered trials

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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.