SENSITIVITY TO ETHANOL-INDUCED ATAXIA IN HOT AND COLD SELECTED LINES OF MICE

Studies with inbred strains of mice have suggested that there may be a genetic correlation between strain sensitivities to the ataxic and hy pothermic responses to ethanol (EtOH), which would suggest that some g enes influence both responses. To test this hypothesis, EtOH sensitivi ty was determined in replicate lines of mice selectively bred for sens itivity (COLD) or resistance (HOT) to acute ethanol hypothermia. Sever al tests were used to index ataxia, related traits such as muscle stre ngth, and locomotor activity. The screen test yielded a dose-dependent EtOH-induced decrease in performance that did not differ between the selected lines. Based on the dose-response characteristics of this tas k, 2.5 g/kg of EtOH was used as the test dose for the remaining experi ments. Results from the fixed-speed rotarod and the grid test of motor incoordination also indicated no significant differences between HOT and COLD mice in sensitivity to EtOH impairment. When the selected lin es were tested on an accelerating rotarod, COLD mice were impaired by the acute EtOH injection, but HOT mice were unaffected. COLD mice were more sensitive to EtOH-induced decrements in grip strength and locomo tor activity. Overall, the results indicated that HOT and COLD mice we re only differentially sensitive to EtOH in some tasks related to atax ia, suggesting that some genes must be associated uniquely with EtOH-i nduced hypothermia or ataxia. The mixed results from the various tests indicate that ataxia can best be conceived as a group of related comp lex behaviors that cannot be assessed adequately by the use of a singl e task and that ataxia-related behaviors are influenced by different g roups of genes.