Evidence map›Paper›PMID 20657349›Full record

ArticlePharmacogenetics and genomics2010

The metabotropic glutamate receptor subtype 5 mediates sensitivity to the sedative properties of ethanol.

Chris Downing, Michael J Marks, Colin Larson, Thomas E Johnson

Abstract read
In one paragraph

Article in Pharmacogenetics and genomics, 2010. 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
1.7field-weighted citation impact, top 18% 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

2 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. 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

4 authors at 1 institution in 1 country.

Chris DowningInstitute for Behavioral Genetics, University of Colorado, Boulder, Colorado, USA. cdowning@pharmacy.isu.edu
Michael J Marks
Colin Larson
Thomas E Johnson
Institute for Behavioral Medicine · US

Funding

Ethanol Teratogenesis and Genomic ImprintingR01AA016676 · NIAAA · UNIVERSITY OF COLORADO · PI JOHNSON, THOMAS E. · 2006 to 2010
$2.1M
NIAAA NIH HHS AA01466NIAAA NIH HHS AA016676NIAAA NIH HHS L40 AA017033NIAAA NIH HHS R01 AA016676
6 · The paper itself

Abstract

objectiveInbred long-sleep and short-sleep mice (ILS and ISS) were selectively bred for differential sensitivity to the sedative effects of ethanol. Lines of mice derived from these progenitors have been used to identify several quantitative trait loci (QTLs) mediating loss of the righting reflex due to ethanol (LORE). This study investigated the metabotropic glutamate receptor subtype 5 (mGluR5) as a candidate gene underlying Lore7, a QTL mediating differential LORE sensitivity.

methodsWe used knockout mice, a quantitative complementation test, pharmacological antagonism of mGluR5, real-time quantitative PCR, radioligand binding, DNA sequencing, and bioinformatics to examine the role of mGluR5 in ethanol-induced sedation.

resultsmGluR5 knockout mice had a significantly longer LORE duration than wildtype controls. Administration of the mGluR5 antagonist 2-methyl-6-(phenylethyl)-pyridine (MPEP) had differential effects on LORE in ILS and ISS mice. A quantitative complementation test also supported mGluR5 mediating LORE. Two intronic single-nucleotide polymorphisms in mGluR5 were highly correlated with LORE in recombinant inbred mice derived from a cross between ILS and ISS (LXS RIs). Differences in mGluR5 mRNA level and receptor density were observed between ILS and ISS in distinct brain regions. Finally, data from WebQTL showed that mGluR5 expression was highly correlated with several LORE phenotypes in the LXS RIs.

conclusionAltogether, this data provides convincing evidence that mGluR5 mediates differential sensitivity to the sedative effects of ethanol. Studies from the human literature have also identified mGluR5 as a potential candidate gene for ethanol sensitivity.

Indexed as

AnimalsEthanolFemaleGenetic Complementation TestHippocampusHypnotics and SedativesMaleMicePolymerase Chain ReactionPolymorphism, Single NucleotidePyridinesQuantitative Trait LociRadioligand AssayReceptor, Metabotropic Glutamate 5Receptors, Metabotropic GlutamateReflex6-methyl-2-(phenylethynyl)pyridineEthanolGRM5 protein, humanGrm5 protein, mouseHypnotics and SedativesPyridinesReceptor, Metabotropic Glutamate 5Receptors, Metabotropic GlutamateAlcoholLoss of Righting ReflexmGluR5MPEPQuantitative Complementation

Identifiers

PMID20657349
PMCPMC2933419
OpenAlexW2000356101

What OpenQuestion holds

Textmetadata
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.