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 hypothermic responses to ethanol (EtOH), which would suggest that some genes influence both responses. To test this hypothesis, EtOH sensitivity was determined in replicate lines of mice selectively bred for sensitivity (COLD) or resistance (HOT) to acute ethanol hypothermia. Several tests were used to index ataxia, related traits such as muscle strength, 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 task, 2.5 g/kg of EtOH was used as the test dose for the remaining experiments. 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 lines 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 locomotor activity. Overall, the results indicated that HOT and COLD mice were only differentially sensitive to EtOH in some tasks related to ataxia, suggesting that some genes must be associated uniquely with EtOH-induced hypothermia or ataxia. The mixed results from the various tests indicate that ataxia can best be conceived as a group of related complex behaviors that cannot be assessed adequately by the use of a single task and that ataxia-related behaviors are influenced by different groups of genes.
Schafer
G L
GL
Research Service, Veterans Affairs Medical Center, Portland, OR 97201, USA.
Crabbe
J C
JC
D000435:Alcoholic Intoxication / Q000235:genetics; D000437:Alcoholism / Q000235:genetics; D000818:Animals; D001259:Ataxia / Q000139:chemically induced* / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D020022:Genetic Predisposition to Disease; D018737:Hand Strength / Q000502:physiology; D007035:Hypothermia / Q000139:chemically induced / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D010597:Pharmacogenetics; D013045:Species Specificity
D000431:Ethanol