Evidence map›Paper›PMID 39505853›Full record

ArticleTranslational psychiatry2024

Distinct Chrna5 mutations link excessive alcohol use to types I/II vulnerability profiles and IPN GABAergic neurons.

Léa Tochon, Nadia Henkous, Morgane Besson, Uwe Maskos, Vincent David

Abstract read
In one paragraph

Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Disruption ofiScience · 2026
    Article
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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Léa TochonUniv. Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux, France. lea.tochon.neuro@gmail.com.ORCID 0000-0001-6566-6661
Nadia HenkousUniv. Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux, France.
Morgane BessonInstitut Pasteur, Université Paris Cité, CNRS UMR 3571, Integrative Neurobiology of Cholinergic Systems, Paris, France.
Uwe MaskosInstitut Pasteur, Université Paris Cité, CNRS UMR 3571, Integrative Neurobiology of Cholinergic Systems, Paris, France.ORCID 0000-0002-2029-1437
Vincent DavidUniv. Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux, France. vincent.david@u-bordeaux.fr.

Funding

Agence Nationale de la Recherche (French National Research Agency) ANR-11IDEX- 0004-02Fondation pour la Recherche Médicale (Foundation for Medical Research in France) FRM Equipe 2019Institut National Du Cancer (French National Cancer Institute) INCa/CANCEROPOLE-TABAC-01-16022
6 · The paper itself

Abstract

Genome wide association and animal studies have implicated genetic variations in CHRNΑ5, encoding the α5 subunit-containing nicotinic acetylcholine receptors (α5*nAChRs), as a risk factor for developing alcohol use disorders (AUDs). To understand how α5*nAChR mutations may influence alcohol (EtOH) drinking behavior, we used a two-bottle choice procedure with intermittent access to alcohol in male and female transgenic mice expressing either the highly frequent human single nucleotide polymorphism (α5SNP/rs16969968) or a deletion of the Chrna5 gene (α5KO). AUDs-related preconsommatory traits (anxiety, sensation-seeking and impulsivity) were assessed with a battery of relevant tasks (elevated-plus maze, novel place preference and step-down inhibitory avoidance). The implication of the α5-expressing IPN GABAergic neurons in AUDs and related behavioral traits was verified using neurospecific lentiviral (LV)-induced reexpression of the α5 subunit in α5KOxGAD-Cre mice. Both α5SNP and α5KO mice showed over-consumption of EtOH, but displayed opposite vulnerability profiles consistent with Cloninger's subtypes of human AUDs. α5SNP mice showed Type I-like characteristics, i.e., high anxiety, novelty avoidance, whereas α5KOs exhibited Type II-like features such as low anxiety and high impulsivity. LV re-expression of the α5 subunit in IPN GABAergic neurons restored the control of EtOH intake and improved the impulsive phenotype. We demonstrate that the SNP (rs16969968) or null mutation of Chrna5 result in increased volitional EtOH consumption but opposite effects on anxiety, novelty-seeking and impulsive-like behaviors that match Cloninger type I and II of AUDs, including sex-related variations. IPN GABAergic neurons expressing α5*nAChRs play a key role in limiting both EtOH drinking and motor impulsivity.

Indexed as

AlcoholismGABAergic NeuronsPolymorphism, Single NucleotideReceptors, NicotinicAlcohol DrinkingAnimalsAnxietyBehavior, AnimalEthanolFemaleHumansImpulsive BehaviorMaleMiceMice, KnockoutMice, TransgenicCHRNA5 protein, humanCHRNA5 protein, mouseEthanolNerve Tissue ProteinsReceptors, Nicotinic

Identifiers

PMID39505853
PMCPMC11541707

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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.