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J Appl Physiol (March 19, 2004). doi:10.1152/japplphysiol.00086.2004
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Submitted on January 27, 2004
Accepted on March 15, 2004

Observer-rated ataxia: Rating scales for assessment of genetic differences in ethanol-induced intoxication in mice

Pamela Metten1*, Karyn L Best1, Andy J Cameron1, Alisha B Saultz1, Jessica M Zuraw1, Chia-Hua Yu1, Douglas Wahlsten2, and John C Crabbe1

1 Department of Veterans Affairs Medical Center, Portland Alcohol Research Center, Portland, OR, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA
2 Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA

* To whom correspondence should be addressed. E-mail: mettenp{at}ohsu.edu.

Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance would 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, 3.25 g/kg) in 9 inbred mouse strains. Each scale independently rates a single behavior. Raters, blind to dose, scored four behaviors (splay of hind legs, wobbling, nose down, belly drag) at each of four time points following injection. The severities of hind leg splaying and wobbling were quantifiable, while nose down and belly dragging were expressed in all-or-none fashion. Inter-rater reliabilities were substantial (.75 <= r <= .99). Splay scores (rated 0 - 5) displayed significant effects of strain, dose, and time point. Wobbling (rated 0 - 4) was dependent upon strain and time point. Ethanol affected wobbling (most strains scored greater than 0 at some times), 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.




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