Characterization of the parallel rod floor apparatus to test motor incoordination in mice

Abstract

Impairment of motor coordination, or ataxia, is a prominent effect of alcohol ingestion in humans. To date, many models have been created to examine this phenomenon in animals. Evidence suggests that the tasks thought to measure this behavior in mice actually measure different components of this complex trait. We have characterized the parallel rod floor apparatus to quantify ethanol-induced motor incoordination. Using genetically heterogeneous mice, we evaluated the influence of rod diameter and inter-rod distance on doserelated ethanol-induced motor incoordination to select parameters that optimized testing procedures. We then used the DBA/2J and C57BL/6J inbred strains of mice to examine the effect of 2 g/kg of ethanol, by serially testing mice on two floor types, separated by 1 week. Finally, we tested eight inbred strains of mice on four floor types to examine patterns of strain sensitivity to 2 g/kg of intraperitoneal ethanol and determined the test parameters that maximized strain effect size. Motor incoordination varied depending on the floor type and strain. When data from strain 129S1/SvlmJ were removed from the analyses because of their extreme behavior, the greatest strain effect size was observed on one floor type during the first 10 min of testing after 2 g/kg of intraperitoneal ethanol. These findings suggest that the parallel rod floor apparatus provides a useful means for examining ethanol-induced motor incoordination in mice but that specific testing procedures are important for optimizing detection of motor incoordination and genetic influences.

The parallel rod floor test: a measure of ataxia in mice

“…In our published data for inbred strains, experiments 3 and 4 included repeated testing of the animals on the same or different floor types. We saw reasonable test-retest reliability in the former case, and the same patterns of strain differences in the latter, which suggests that repeated testing on the parallel rod floor apparatus should be feasible 17 .…”

“…We recommend using a ratio (errors per cm traveled  100) to index ataxia in this apparatus corrected for individual differences in activity. In a panel of eight inbred strains, we observed ataxia ratios ranging from 7 to 112 across all animals tested, with strain means ranging from 18 to 39 after 2 g kg -1 ethanol (individual strain means can be obtained by visiting The Jackson Laboratory's Mouse Phenome Database, http://phenome.jax.org/pub-cgi/phenome/mpdcgi?rtn¼docs/home) 17 ; mice given higher doses of alcohol or mutants with greater impairment of motor coordination may show higher ataxia ratios. We used 2 d of habituation to the effects of saline in this test before testing for drug effects.…”

“…(The grid test shares this advantage with the parallel rod floor test.) Overall, when we compared eight inbred strains of mice for ethanol sensitivity across four floor types, our results suggested that the parallel rod floor test is a reliable and robust measure of genetic contributions to ethanol-induced locomotor incoordination because all variants of the test yielded a similar strain sensitivity pattern 17 . This is in contrast to several other measures of ataxia, such as the rotarod, where the parameters of the task (e.g., rate of acceleration of rotation) have been shown to have large effects on the pattern of strain sensitivity.…”

“…The task also will need to be validated for use with cerebellar mutant mice and genetically engineered genotypes that may have a more extreme ataxia. For example, the random hole alley test was reportedly sensitive to extreme ataxia in staggerer mutant mice 5 , but we were unable to adapt this apparatus to be sensitive to the modestly intoxicating effects of ethanol 17 . Another aspect of this potential limitation is that certain genotypes of mice behave extremely in the parallel rod floor test but not in other tasks that assess ataxia.…”

“…Finally, the original grid test also was sensitive to intoxication induced by sodium pentobarbital 3 . We have developed a new mouse model of motor incoordination that combines the positive features of the grid test and the paw slip test, and we call it the parallel rod floor test 17 (Fig. 1).…”