An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice

Pamela Metten, Jason P. Schlumbohm, Lawrence C. Huang, Gian D. Greenberg, Wyatt R. Hack, Stephanie E. Spence, John C. Crabbe

Research output: Contribution to journalArticle

  • 1 Citations

Abstract

Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes.

LanguageEnglish (US)
Pages19-35
Number of pages17
JournalAlcohol
Volume68
DOIs
StatePublished - May 1 2018

Fingerprint

test battery
Behavioral Symptoms
withdrawal
alcohol
Alcohols
Ethanol
Anxiety
Anhedonia
Gene Components
Substance Withdrawal Syndrome
Genes
Vapors
Hypothermia
Tremor
Individuality
Inhalation
Alcoholism
Walking
Sucrose
Tail

Keywords

  • Alcohol withdrawal syndrome
  • Behavioral domains
  • Mouse
  • Test battery

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Cite this

Metten, P., Schlumbohm, J. P., Huang, L. C., Greenberg, G. D., Hack, W. R., Spence, S. E., & Crabbe, J. C. (2018). An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice. Alcohol, 68, 19-35. https://doi.org/10.1016/j.alcohol.2017.08.014

An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice. / Metten, Pamela; Schlumbohm, Jason P.; Huang, Lawrence C.; Greenberg, Gian D.; Hack, Wyatt R.; Spence, Stephanie E.; Crabbe, John C.

In: Alcohol, Vol. 68, 01.05.2018, p. 19-35.

Research output: Contribution to journalArticle

Metten, P, Schlumbohm, JP, Huang, LC, Greenberg, GD, Hack, WR, Spence, SE & Crabbe, JC 2018, 'An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice' Alcohol, vol. 68, pp. 19-35. https://doi.org/10.1016/j.alcohol.2017.08.014
Metten P, Schlumbohm JP, Huang LC, Greenberg GD, Hack WR, Spence SE et al. An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice. Alcohol. 2018 May 1;68:19-35. https://doi.org/10.1016/j.alcohol.2017.08.014
Metten, Pamela ; Schlumbohm, Jason P. ; Huang, Lawrence C. ; Greenberg, Gian D. ; Hack, Wyatt R. ; Spence, Stephanie E. ; Crabbe, John C. / An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice. In: Alcohol. 2018 ; Vol. 68. pp. 19-35.
@article{cec1d9887f4949ac9bfd9c0d912d4ef0,
title = "An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice",
abstract = "Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes.",
keywords = "Alcohol withdrawal syndrome, Behavioral domains, Mouse, Test battery",
author = "Pamela Metten and Schlumbohm, {Jason P.} and Huang, {Lawrence C.} and Greenberg, {Gian D.} and Hack, {Wyatt R.} and Spence, {Stephanie E.} and Crabbe, {John C.}",
year = "2018",
month = "5",
day = "1",
doi = "10.1016/j.alcohol.2017.08.014",
language = "English (US)",
volume = "68",
pages = "19--35",
journal = "Alcohol",
issn = "0741-8329",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice

AU - Metten, Pamela

AU - Schlumbohm, Jason P.

AU - Huang, Lawrence C.

AU - Greenberg, Gian D.

AU - Hack, Wyatt R.

AU - Spence, Stephanie E.

AU - Crabbe, John C.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes.

AB - Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes.

KW - Alcohol withdrawal syndrome

KW - Behavioral domains

KW - Mouse

KW - Test battery

UR - http://www.scopus.com/inward/record.url?scp=85041421993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041421993&partnerID=8YFLogxK

U2 - 10.1016/j.alcohol.2017.08.014

DO - 10.1016/j.alcohol.2017.08.014

M3 - Article

VL - 68

SP - 19

EP - 35

JO - Alcohol

T2 - Alcohol

JF - Alcohol

SN - 0741-8329

ER -