PMID- 29427828
OWN - NLM
STAT- MEDLINE
DCOM- 20190925
LR  - 20190925
IS  - 1873-6823 (Electronic)
IS  - 0741-8329 (Print)
IS  - 0741-8329 (Linking)
VI  - 68
DP  - 2018 May
TI  - An alcohol withdrawal test battery measuring multiple behavioral symptoms in 
      mice.
PG  - 19-35
LID - S0741-8329(17)30847-9 [pii]
LID - 10.1016/j.alcohol.2017.08.014 [doi]
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.
CI  - Published by Elsevier Inc.
FAU - Metten, Pamela
AU  - Metten P
AD  - VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon 
      Health & Science University, Portland, Oregon, USA. Electronic address: 
      mettenp@ohsu.edu.
FAU - Schlumbohm, Jason P
AU  - Schlumbohm JP
AD  - VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon 
      Health & Science University, Portland, Oregon, USA.
FAU - Huang, Lawrence C
AU  - Huang LC
AD  - VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon 
      Health & Science University, Portland, Oregon, USA.
FAU - Greenberg, Gian D
AU  - Greenberg GD
AD  - VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon 
      Health & Science University, Portland, Oregon, USA.
FAU - Hack, Wyatt R
AU  - Hack WR
AD  - VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon 
      Health & Science University, Portland, Oregon, USA.
FAU - Spence, Stephanie E
AU  - Spence SE
AD  - VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon 
      Health & Science University, Portland, Oregon, USA.
FAU - Crabbe, John C
AU  - Crabbe JC
AD  - VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon 
      Health & Science University, Portland, Oregon, USA.
LA  - eng
GR  - I01 BX000313/BX/BLRD VA/United States
GR  - R24 AA020245/AA/NIAAA NIH HHS/United States
GR  - U01 AA013519/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20170906
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
RN  - 0 (Central Nervous System Depressants)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Administration, Inhalation
MH  - Alcohol Withdrawal Seizures/genetics
MH  - Animals
MH  - Anxiety/chemically induced/psychology
MH  - Ataxia/chemically induced/psychology
MH  - *Behavior, Animal
MH  - *Central Nervous System Depressants/administration & dosage/blood
MH  - Depression/psychology
MH  - *Ethanol/administration & dosage/blood
MH  - Female
MH  - Individuality
MH  - Male
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Pain Measurement/drug effects
MH  - Species Specificity
MH  - Substance Withdrawal Syndrome/genetics/*psychology
PMC - PMC5839916
MID - NIHMS904334
OTO - NOTNLM
OT  - Alcohol withdrawal syndrome
OT  - Behavioral domains
OT  - Mouse
OT  - Test battery
COIS- All authors report no conflicts of interest.
EDAT- 2018/02/11 06:00
MHDA- 2019/09/26 06:00
PMCR- 2019/05/01
CRDT- 2018/02/11 06:00
PHST- 2017/08/04 00:00 [received]
PHST- 2017/08/30 00:00 [revised]
PHST- 2017/08/31 00:00 [accepted]
PHST- 2018/02/11 06:00 [pubmed]
PHST- 2019/09/26 06:00 [medline]
PHST- 2018/02/11 06:00 [entrez]
PHST- 2019/05/01 00:00 [pmc-release]
AID - S0741-8329(17)30847-9 [pii]
AID - 10.1016/j.alcohol.2017.08.014 [doi]
PST - ppublish
SO  - Alcohol. 2018 May;68:19-35. doi: 10.1016/j.alcohol.2017.08.014. Epub 2017 Sep 6.