title: Observer-rated ataxia: rating scales for assessment of genetic differences in ethanol-induced intoxication in mice.
abstract: Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance could be aided by the existence of a simple observation-based rating scale of ataxia for mice. Rating scales were developed to assess ataxia after ethanol (2.75, 3.0, and 3.25 g/kg) in nine inbred mouse strains. Each scale independently rates a single behavior. Raters, blinded to dose, scored four behaviors (splay of hind legs, wobbling, nose down, and belly drag) at each of four time points after injection. The severities of hind leg splaying and wobbling were quantifiable, whereas nose down and belly dragging were expressed in all-or-none fashion. Interrater reliabilities were substantial (0.75 <or= r <or= 0.99). Splay scores (rated 0-5) displayed significant effects of strain, dose, and time point. Wobbling (rated 0-4) was dependent on strain and time point. Ethanol affected wobbling (most strains scored >0 at some time), but all doses were equally effective. Incidence of nose down and belly dragging behaviors increased strain dependently after ethanol, but strains did not differentially respond to dose. Ethanol-induced splaying was modestly, and negatively, genetically correlated with wobbling. Nose down and belly dragging tended to be associated with splaying and wobbling at later times. Four distinct ataxia-related behaviors were sensitive to ethanol. Strains differed in ethanol sensitivity for all measures. Modest strain mean correlations among behaviors indicate that these behaviors are probably under control of largely different genes and that ataxia rating scales should rate separate behaviors on discrete scales.
authors.affiliation: Department of Veterans Affairs Medical Center, Oregon Health & Science University, Portland, Oregon 97239, USA. mettenp@ohsu.edu
authors.forename: Pamela
authors.initials: P
authors.lastname: Metten
authors.forename: Karyn L
authors.initials: KL
authors.lastname: Best
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Cameron
authors.forename: Alisha B
authors.initials: AB
authors.lastname: Saultz
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Zuraw
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Yu
authors.forename: Douglas
authors.initials: D
authors.lastname: Wahlsten
authors.forename: John C
authors.initials: JC
authors.lastname: Crabbe
mesh_terms: D000435:Alcoholic Intoxication / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D020234:Gait Ataxia / Q000139:chemically induced* / Q000235:genetics* / Q000523:psychology; D006614:Hindlimb / Q000502:physiology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015588:Observer Variation; D010641:Phenotype; D004856:Postural Balance / Q000187:drug effects; D011187:Posture / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D013045:Species Specificity
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol