the magnitude of tolerance to ethanol hypothermia49 or to the duration of loss of righting reflex.50 Third, 20–27 recombinant inbred strains created from the DBA/2J and C57BL/6J mouse strains have been examined for several phenotypes that reflect alcohol tolerance and severity of withdrawal. Severity of acute withdrawal (Metten and Belknap, unpublished data) was not correlated significantly with tolerance to ethanol-induced hypothermia,51,52 ataxia in the grid test,53 or two different measures of acute functional tolerance on a dowel balancing test.54,55 For chronic withdrawal, however, there were significant positive correlations with both dowel test tolerance outcomes but not with the other measures of tolerance. In summary, across the three approaches that have examined this question, the rodent literature is congruent with our findings in humans that genetic risk factors for tolerance to alcohol and alcohol-induced withdrawal are weakly inter-related.45
