Ethanol withdrawal-induced motor impairment in mice
Human ethanol withdrawal manifests as multiple behavioral deficits with distinct time courses. Most studies with mice index ethanol withdrawal severity with the handling-induced convulsion (HIC). Using the accelerating rotarod (ARR), we recently showed that ethanol withdrawal produced motor impairment.
This study aimed (a) to characterize further the ARR withdrawal trait, (b) to assess generalizability across additional behavioral assays, and (c) to test the genetic correlation between ethanol withdrawal ARR impairment and HICs.
The severity of the ARR performance deficit depends on ethanol vapor dose and exposure duration, and lasts 1–4 days. Fatigue could not explain the deficits, which were also evident after intermittent exposure to ethanol vapor. Withdrawing mice were also impaired on a balance beam, but not on a static dowel or in foot slip errors per distance traveled in the parallel rod floor test, where they showed reduced locomotor activity. To assess genetic influences, we compared Withdrawal Seizure-Prone and -Resistant mice, genetically selected to express severe vs. mild withdrawal HICs, respectively. The ARR scores were approximately equivalent in all groups treated with ethanol vapor, though Withdrawal Seizure-Prone (WSP) mice may have displayed a slightly more severe deficit as control-treated WSP mice performed better than control-treated Withdrawal Seizure-Resistant mice.
These studies show that ethanol withdrawal motor impairment is sensitive to a range of ethanol doses and lasts for several days. Multiple assays of behavioral impairment are affected, but the effects depend on the assay employed. Genetic contributions to withdrawal-induced ARR impairment appear largely distinct from those leading to severe or mild HICs.
KeywordsEthanol withdrawal Mouse Vapor inhalation Rotarod WSP- and WSR-selected lines Motor impairment
Support for this work was from the NIH (AA010760, AA013519, T32AA05828, and F32AA17021) and a grant from the US Department of Veterans Affairs. Association for Assessment and Accreditation of Laboratory Animal Care International principles of laboratory animal care were followed, as well as the Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (National Research Council 2003). The experiments comply with the current laws of the USA. We thank Lauren Brown and Stephanie Spence for assistance with the experiments, and Mark Rutledge-Gorman for assistance with the manuscript.
Conflicts of interest
The authors have no conflicts of interest to declare.
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