We predicted that the internal concentration of ethanol would be higher in animals in which ethanol metabolism is compromised. We determined the effect of inactivation of the two ADHs both singly and in combination on the accumulation of ethanol at the dose of exogenous ethanol at which we tested behavior, 400 mM. We determined the internal ethanol concentration after 10 and 50 minutes of ethanol exposure, to observe an acute accumulation of ethanol (10 minutes) as well as accumulation that could potentially be altered by the development of acute tolerance (50 minutes). Loss of sodh-1 significantly increased the internal ethanol concentration in animals relative to wild type (Figure 2c). However, inactivation of H24K24.3 did not significantly increase the internal ethanol concentration (Figure 2c). Interestingly, when we examined animals in which both ADHs were inactivated, sodh-1(ok2799);H24K24.3(RNAi), the concentration of ethanol that the animals accumulated was similar to that of wild type at 10 minutes (Figure 2c), suggesting the possibility that loss of H24K24.3 may trigger a compensatory response that minimizes the effect seen for loss of sodh-1 alone.
