Evidence map›Paper›PMID 25662840›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015

KCNN Genes that Encode Small-Conductance Ca2+-Activated K+ Channels Influence Alcohol and Drug Addiction.

Audrey E Padula, William C Griffin, Marcelo F Lopez, Sudarat Nimitvilai, Reginald Cannady, Natalie S McGuier, Elissa J Chesler, Michael F Miles, Robert W Williams, Patrick K Randall and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. KAlcohol (Fayetteville, N.Y.) · 2025
    Article
  6. Article
  7. Adaptations in glutathione-based redox protein signaling pathways and alcohol drinking across species.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. KBiomedicines · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Potassium Channels and Their Potential Roles in Substance Use Disorders.International journal of molecular sciences · 2021
    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

13 authors at 4 institutions in 1 country.

Audrey E PadulaDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
William C GriffinDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Marcelo F LopezDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Sudarat NimitvilaiDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Reginald CannadyDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Natalie S McGuierDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Elissa J CheslerThe Jackson Laboratory, Bar Harbor, Maine, USA.ORCID 0000000256425062
Michael F MilesVirginia Commonwealth University, Richmond, VA, USA.
Robert W WilliamsUniversity of Tennessee Health Sciences Center, Memphis, TN, USA.
Patrick K RandallDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
John J WoodwardDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Howard C BeckerDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Patrick J MulhollandDepartment of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Medical University of South Carolina · USJackson Laboratory · USUniversity of Tennessee Health Science Center · USVirginia Commonwealth University · US

Funding

TREATING ETHANOL WITHDRAWAL WITH LORAZEPAM/NALTREXONEP50AA010761 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HOWARD C. BECKER · 1996 to 2026
$46.8M
Project 5 - Genetic architecture of alcohol use disorder using cross-trait genetic correlations and public next-generation sequencing studiesP50AA022537 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI JILL C BETTINGER · 2014 to 2026
$19.6M
Ethanol Dependence &Stress Effects on Ethanol DrinkingU01AA014095 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI HOWARD C. BECKER · 2003 to 2026
$9.0M
TRAINING IN ALCOHOL TREATMENT RESEARCHT32AA007474 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI John J. Woodward · 1987 to 2026
$8.5M
Systems Genetics of Alcohol Response and Stress Effects in CNSU01AA013499 · NIAAA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI WILLIAMS, ROBERT W. · 2002 to 2016
$4.8M
Data Structures, Algorithms and Tools for Ontological DiscoveryR01AA018776 · NIAAA · JACKSON LABORATORY · PI CHESLER, ELISSA J · 2010 to 2019
$3.9M
Ethanol Sensitivity of Native and Cloned NMDA ReceptorsR37AA009986 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI WOODWARD, JOHN J. · 2009 to 2018
$3.8M
INIA-STRESS: Informatics and Analysis CoreU01AA016662 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI WILLIAMS, ROBERT W. · 2007 to 2016
$2.9M
Stress and Ethanol Dependence: SK Channels and GlutamateU01AA020930 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MULHOLLAND, PATRICK J. · 2012 to 2021
$2.6M
Of Mice and Primates: Gene Networks in Excessive Ethanol Consumption and AnxietyU01AA016667 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI MILES, MICHAEL F · 2007 to 2016
$2.4M
ETHANOL SENSITIVITY OF NATIVE AND CLONED NMDA RECEPTORSR01AA009986 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI WOODWARD, JOHN J. · 1995 to 2009
$2.0M
Mouse Chronic Intermittent Ethanol (CIE) CoreU01AA020929 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI LOPEZ, MARCELO F. · 2012 to 2015
$1.5M
NIAAA NIH HHS AA009986NIAAA NIH HHS AA010761NIAAA NIH HHS AA013499NIAAA NIH HHS AA014095NIAAA NIH HHS AA016662NIAAA NIH HHS AA016667NIAAA NIH HHS AA018776NIAAA NIH HHS AA020929NIAAA NIH HHS AA020930NIAAA NIH HHS P50 AA010761NIAAA NIH HHS P50 AA022537NIAAA NIH HHS R01 AA009986NIAAA NIH HHS R01 AA018776NIAAA NIH HHS R01 AA020634NIAAA NIH HHS R37 AA009986NIAAA NIH HHS T32 AA007474NIAAA NIH HHS U01 AA013499NIAAA NIH HHS U01 AA014095NIAAA NIH HHS U01 AA016662NIAAA NIH HHS U01 AA016667NIAAA NIH HHS U01 AA020929NIAAA NIH HHS U01 AA020930NIAAA NIH HHS U24 AA020929
6 · The paper itself

Abstract

Small-conductance Ca(2+)-activated K(+) (KCa2) channels control neuronal excitability and synaptic plasticity, and have been implicated in substance abuse. However, it is unknown if genes that encode KCa2 channels (KCNN1-3) influence alcohol and drug addiction. In the present study, an integrative functional genomics approach shows that genetic datasets for alcohol, nicotine, and illicit drugs contain the family of KCNN genes. Alcohol preference and dependence QTLs contain KCNN2 and KCNN3, and Kcnn3 transcript levels in the nucleus accumbens (NAc) of genetically diverse BXD strains of mice predicted voluntary alcohol consumption. Transcript levels of Kcnn3 in the NAc negatively correlated with alcohol intake levels in BXD strains, and alcohol dependence enhanced the strength of this association. Microinjections of the KCa2 channel inhibitor apamin into the NAc increased alcohol intake in control C57BL/6J mice, while spontaneous seizures developed in alcohol-dependent mice following apamin injection. Consistent with this finding, alcohol dependence enhanced the intrinsic excitability of medium spiny neurons in the NAc core and reduced the function and protein expression of KCa2 channels in the NAc. Altogether, these data implicate the family of KCNN genes in alcohol, nicotine, and drug addiction, and identify KCNN3 as a mediator of voluntary and excessive alcohol consumption. KCa2.3 channels represent a promising novel target in the pharmacogenetic treatment of alcohol and drug addiction.

Indexed as

AlcoholismAnalysis of VarianceAnimalsApaminCentral Nervous System DepressantsChoice BehaviorComputational BiologyConditioning, OperantDose-Response Relationship, DrugElectric StimulationEthanolFemaleHumansIn Vitro TechniquesLinear ModelsMaleApaminCentral Nervous System DepressantsEthanolPotassium Channel BlockersSmall-Conductance Calcium-Activated Potassium Channels

Identifiers

PMID25662840
PMCPMC4839516
OpenAlexW2025655232

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.