Assessment of genetic susceptibility to ethanol intoxication in mice

Nathan R. Rustay, Douglas Wahlsten, John Jr Crabbe

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Increased use of gene manipulation in mice (e.g., targeted or random mutagenesis) has been accompanied by increased reliance on a very few rapid and simple behavioral assays, each of which aspires to model a human behavioral domain. Yet, each assay comprises multiple traits, influenced by multiple genetic factors. Motor incoordination (ataxia), a common characteristic of many neurological disorders, may reflect disordered balance, muscle strength, proprioception, and/or patterned gait. Impaired motor performance can confound interpretation of behavioral assays of learning and memory, exploration, motivation, and sensory competence. The rotarod is one of the most commonly used tests to measure coordination in mice. We show here that exactly how the rotarod test is performed can markedly alter the apparent patterns of genetic influence both in undrugged performance and sensitivity to ethanol intoxication. However, when tested with well chosen parameters, the accelerating rotarod test showed very high inter- and intralaboratory reliability. Depending on test conditions, ethanol can either disrupt or enhance performance in some strains. Genetic contribution to performance on the accelerating versus the fixed-speed rotarod assay can be completely dissociated under some test conditions, and multiple test parameters are needed to assess the range of genetic influence adequately.

Original languageEnglish (US)
Pages (from-to)2917-2922
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number5
DOIs
StatePublished - Mar 4 2003

Fingerprint

Rotarod Performance Test
Genetic Predisposition to Disease
Ethanol
Ataxia
Proprioception
Muscle Strength
Nervous System Diseases
Gait
Mutagenesis
Mental Competency
Motivation
Learning
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Assessment of genetic susceptibility to ethanol intoxication in mice. / Rustay, Nathan R.; Wahlsten, Douglas; Crabbe, John Jr.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 5, 04.03.2003, p. 2917-2922.

Research output: Contribution to journalArticle

@article{fc28ca5574b04942a046f02da00687d2,
title = "Assessment of genetic susceptibility to ethanol intoxication in mice",
abstract = "Increased use of gene manipulation in mice (e.g., targeted or random mutagenesis) has been accompanied by increased reliance on a very few rapid and simple behavioral assays, each of which aspires to model a human behavioral domain. Yet, each assay comprises multiple traits, influenced by multiple genetic factors. Motor incoordination (ataxia), a common characteristic of many neurological disorders, may reflect disordered balance, muscle strength, proprioception, and/or patterned gait. Impaired motor performance can confound interpretation of behavioral assays of learning and memory, exploration, motivation, and sensory competence. The rotarod is one of the most commonly used tests to measure coordination in mice. We show here that exactly how the rotarod test is performed can markedly alter the apparent patterns of genetic influence both in undrugged performance and sensitivity to ethanol intoxication. However, when tested with well chosen parameters, the accelerating rotarod test showed very high inter- and intralaboratory reliability. Depending on test conditions, ethanol can either disrupt or enhance performance in some strains. Genetic contribution to performance on the accelerating versus the fixed-speed rotarod assay can be completely dissociated under some test conditions, and multiple test parameters are needed to assess the range of genetic influence adequately.",
author = "Rustay, {Nathan R.} and Douglas Wahlsten and Crabbe, {John Jr}",
year = "2003",
month = "3",
day = "4",
doi = "10.1073/pnas.0437273100",
language = "English (US)",
volume = "100",
pages = "2917--2922",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5",

}

TY - JOUR

T1 - Assessment of genetic susceptibility to ethanol intoxication in mice

AU - Rustay, Nathan R.

AU - Wahlsten, Douglas

AU - Crabbe, John Jr

PY - 2003/3/4

Y1 - 2003/3/4

N2 - Increased use of gene manipulation in mice (e.g., targeted or random mutagenesis) has been accompanied by increased reliance on a very few rapid and simple behavioral assays, each of which aspires to model a human behavioral domain. Yet, each assay comprises multiple traits, influenced by multiple genetic factors. Motor incoordination (ataxia), a common characteristic of many neurological disorders, may reflect disordered balance, muscle strength, proprioception, and/or patterned gait. Impaired motor performance can confound interpretation of behavioral assays of learning and memory, exploration, motivation, and sensory competence. The rotarod is one of the most commonly used tests to measure coordination in mice. We show here that exactly how the rotarod test is performed can markedly alter the apparent patterns of genetic influence both in undrugged performance and sensitivity to ethanol intoxication. However, when tested with well chosen parameters, the accelerating rotarod test showed very high inter- and intralaboratory reliability. Depending on test conditions, ethanol can either disrupt or enhance performance in some strains. Genetic contribution to performance on the accelerating versus the fixed-speed rotarod assay can be completely dissociated under some test conditions, and multiple test parameters are needed to assess the range of genetic influence adequately.

AB - Increased use of gene manipulation in mice (e.g., targeted or random mutagenesis) has been accompanied by increased reliance on a very few rapid and simple behavioral assays, each of which aspires to model a human behavioral domain. Yet, each assay comprises multiple traits, influenced by multiple genetic factors. Motor incoordination (ataxia), a common characteristic of many neurological disorders, may reflect disordered balance, muscle strength, proprioception, and/or patterned gait. Impaired motor performance can confound interpretation of behavioral assays of learning and memory, exploration, motivation, and sensory competence. The rotarod is one of the most commonly used tests to measure coordination in mice. We show here that exactly how the rotarod test is performed can markedly alter the apparent patterns of genetic influence both in undrugged performance and sensitivity to ethanol intoxication. However, when tested with well chosen parameters, the accelerating rotarod test showed very high inter- and intralaboratory reliability. Depending on test conditions, ethanol can either disrupt or enhance performance in some strains. Genetic contribution to performance on the accelerating versus the fixed-speed rotarod assay can be completely dissociated under some test conditions, and multiple test parameters are needed to assess the range of genetic influence adequately.

UR - http://www.scopus.com/inward/record.url?scp=0345269756&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345269756&partnerID=8YFLogxK

U2 - 10.1073/pnas.0437273100

DO - 10.1073/pnas.0437273100

M3 - Article

VL - 100

SP - 2917

EP - 2922

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5

ER -