Ethanol withdrawal-induced motor impairment in mice

• Published in: Psychopharmacologia 2012-03, Vol.220 (2), p.367-378
• Main Authors: Philibin, Scott D., Cameron, Andy J., Schlumbohm, Jason P., Metten, Pamela, Crabbe, John C.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Alcohol; Alcohol, Denatured; Animals; Animals, Outbred Strains; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Convulsions; Dose-Response Relationship, Drug; Drug addiction; Ethanol; Ethanol - administration & dosage; Ethanol - adverse effects; Ethanol - blood; Fatigue; Fatigue - physiopathology; Foot; Locomotor activity; Male; Medical sciences; Mice; Mice, Neurologic Mutants; Motor ability; Motor Skills - drug effects; Motor Skills - physiology; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Rodents; Rotarod Performance Test - methods; Seizures (Medicine); Seizures - chemically induced; Seizures - genetics; Species Specificity; Substance Withdrawal Syndrome - blood; Substance Withdrawal Syndrome - genetics; Substance Withdrawal Syndrome - physiopathology; Time Factors; Vapors; Withdrawal
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-011-2483-1

Rationale 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. Objectives 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. Results 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. Conclusions 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.