Evidence map›Paper›PMID 23906006›Full record

ArticleAlcoholism, clinical and experimental research2014

Ethanol administration produces divergent changes in GABAergic neuroactive steroid immunohistochemistry in the rat brain.

Jason B Cook, Ana Maria G Dumitru, Todd K O'Buckley, A Leslie Morrow

Open access · greenAbstract 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 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 9% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
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  4. Review
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  6. Article
  7. Article
  8. Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol.Handbook of experimental pharmacology · 2018
    Article
  9. The Cerebellar GABAHandbook of experimental pharmacology · 2018
    Article
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  11. Review
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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 1 institution in 1 country.

Jason B CookDepartments of Psychiatry and Pharmacology , Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Ana Maria G Dumitru
Todd K O'Buckley
A Leslie Morrow
University of North Carolina at Chapel Hill · US

Funding

UNC ARC Information/Dissemination CoreP60AA011605 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Thomas L. Kash · 2003 to 2026
$46.3M
Supplement to Molecular and Cellular Studies on Alcohol's ActionsT32AA007573 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FULTON T CREWS, Thomas L. Kash · 1997 to 2026
$9.3M
NEUROSTEROIDS AND ETHANOL INTERACTIONSR37AA010564 · NIAAA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MORROW, A LESLIE · 2000 to 2009
$2.7M
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 P60 AA011605NIAAA NIH HHS R37 AA010564NIAAA NIH HHS R37-AA10564NIAAA NIH HHS T32 AA007573NIAAA NIH HHS T32-AA007573NIAAA NIH HHS U01 AA016672NIAAA NIH HHS U01-AA016672NIAAA NIH HHS U01 AA020935
6 · The paper itself

Abstract

backgroundThe 5α-reduced pregnane neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP or allopregnanolone) is a potent positive modulator of GABAA receptors capable of modulating neuronal activity. In rats, systemic ethanol (EtOH) administration increases cerebral cortical and hippocampal levels of 3α,5α-THP, but the effects of EtOH on 3α,5α-THP levels in other brain regions are unknown. There is a large body of evidence suggesting that 3α,5α-THP enhances EtOH sensitivity, contributes to some behavioral effects of EtOH, and modulates EtOH reinforcement and motivation to drink. In this study, we used immunohistochemistry (IHC) to determine EtOH-induced changes in cellular 3α,5α-THP expression in brain regions associated with EtOH actions and responses.

methodsMale Wistar rats were administered EtOH (2 g/kg) or saline intraperitoneally and after 60 minutes transcardially perfused. IHC was performed on free-floating sections (3 to 4 sections/animal/brain region) using an affinity purified anti-3α,5α-THP primary antibody, and immunoreactivity was visualized with 3,3'-diaminobenzidine.

resultsEtOH significantly increased 3α,5α-THP immunoreactivity by 24 ± 6% in the medial prefrontal cortex, 32 ± 12% in the hippocampal Cornu Ammonis area 1 (CA1) pyramidal cell layer, 52 ± 5% in the polymorph cell layer of the dentate gyrus (DG), 44 ± 15% in the bed nucleus of the stria terminalis, and 36 ± 6% in the paraventricular nucleus of the hypothalamus. In contrast, EtOH administration significantly reduced 3α,5α-THP immunoreactivity by 25 ± 5% in the nucleus accumbens "shore" and 21 ± 3% in the central nucleus of the amygdala. No changes were observed in the ventral tegmental area, dorsomedial striatum, granule cell layer of the DG, or the lateral and basolateral amygdala.

conclusionsThe results suggest acute EtOH (2 g/kg) produces divergent, brain region specific, effects on cellular 3α,5α-THP levels. Regional differences in the effects of EtOH suggest there may be regional brain synthesis of 3α,5α-THP independent of the adrenal glands and novel mechanisms that reduce cellular 3α,5α-THP. Regional differences in EtOH-induced changes in 3α,5α-THP levels likely contribute to EtOH effects on neuronal function in brain.

Indexed as

AnimalsBrainEthanolGABA ModulatorsMalePregnanoloneRatsRats, WistarEthanolGABA ModulatorsPregnanolone3α,5α-THPAlcoholAllopregnanoloneNeuroactive SteroidNeurosteroid

Identifiers

PMID23906006
PMCPMC4196317
OpenAlexW2127788740

What OpenQuestion holds

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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.