There is substantial evidence from human studies that an individual's naïve level of ethanol response is a predisposing factor in the development of alcoholism (Heath et al., 1999; Rodriguez et al., 1993; Schuckit et al., 2001; Schuckit, 1994; Volavka et al., 1996). Factors influencing an individual's level of response to ethanol include both acute sensitivity as well as the magnitude and rate of development of acute tolerance during the ethanol exposure (Hu et al., 2008; Ponomarev and Crabbe, 2002). Here we show that altered ethanol metabolism in C. elegans affects the acute sensitivity of the worms but not the development of acute tolerance. First, ethanol tissue concentrations do not decrease during a single constant exposure (Figure 2b), so metabolism is not sufficient to reduce the concentration of ethanol below that seen at an early time point. Therefore, any reduction in the behavioral effects over this time course is likely to be due to compensatory mechanisms that act in the opposite direction to ethanol or directly limit the action of ethanol. Second, ADH mutant animals develop acute tolerance similar to that
