Evidence map›Paper›PMID 26857960›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

Ethanol Regulation of Synaptic GABAA α4 Receptors Is Prevented by Protein Kinase A Activation.

Stephen L Carlson, John Peyton Bohnsack, A Leslie Morrow

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

15 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Regulation of GABAMembranes · 2021
    Review
  8. Article
  9. Histone deacetylases mediate GABANeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Article
  10. Article
  11. Article
  12. Review
  13. Single Ethanol Withdrawal Regulates Extrasynaptic δ-GABAFrontiers in molecular neuroscience · 2018
    Article
  14. Review
  15. Article
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

3 authors at 1 institution in 1 country.

Stephen L CarlsonDepartments of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
John Peyton BohnsackDepartments of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
A Leslie MorrowDepartments of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, North Carolina morrow@med.unc.edu.
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
NIAAA NIH HHS P60 AA011605NIAAA NIH HHS P60-AA11605NIAAA NIH HHS T32 AA007573NIAAA NIH HHS T32-AA007573
6 · The paper itself

Abstract

Ethanol alters GABAA receptor trafficking and function through activation of protein kinases, and these changes may underlie ethanol dependence and withdrawal. In this study, we used subsynaptic fraction techniques and patch-clamp electrophysiology to investigate the biochemical and functional effects of protein kinase A (PKA) and protein kinase C (PKC) activation by ethanol on synaptic GABAA α4 receptors, a key target of ethanol-induced changes. Rat cerebral cortical neurons were grown for 18 days in vitro and exposed to ethanol and/or kinase modulators for 4 hours, a paradigm that recapitulates GABAergic changes found after chronic ethanol exposure in vivo. PKA activation by forskolin or rolipram during ethanol exposure prevented increases in P2 fraction α4 subunit abundance, whereas inhibiting PKA had no effect. Similarly, in the synaptic fraction, activation of PKA by rolipram in the presence of ethanol prevented the increase in synaptic α4 subunit abundance, whereas inhibiting PKA in the presence of ethanol was ineffective. Conversely, PKC inhibition in the presence of ethanol prevented the ethanol-induced increases in synaptic α4 subunit abundance. Finally, we found that either activating PKA or inhibiting PKC in the presence of ethanol prevented the ethanol-induced decrease in GABA miniature inhibitory postsynaptic current decay τ1, whereas inhibiting PKA had no effect. We conclude that PKA and PKC have opposing effects in the regulation of synaptic α4 receptors, with PKA activation negatively modulating, and PKC activation positively modulating, synaptic α4 subunit abundance and function. These results suggest potential targets for restoring normal GABAergic functioning in the treatment of alcohol use disorders.

Indexed as

AnimalsCentral Nervous System DepressantsCerebral CortexColforsinCyclic AMP-Dependent Protein KinasesEnzyme ActivationEnzyme ActivatorsEthanolFemaleMaleNeuronal PlasticityNeuronsPatch-Clamp TechniquesProtein Kinase CProtein Kinase InhibitorsRatsCentral Nervous System DepressantsColforsinCyclic AMP-Dependent Protein KinasesEnzyme ActivatorsEthanolGabra4 protein, ratProtein Kinase CProtein Kinase InhibitorsReceptors, GABA-ARolipram

Identifiers

PMID26857960
PMCPMC4809316
OpenAlexW2288685581

What OpenQuestion holds

Textmetadata
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.