ethanol) (Davies et al., 2004). Repeated measures two-way ANOVA indicated significant effects of time (F(10,120)=14.66, p=0.0244) and genotype (F(3,120)=11.06, p=0.0009) on locomotor behavior in the presence of ethanol with no interaction between the factors (F(10,120)=1.78, p=0.177). Worms harboring exc-4(rh133), a null allele (Berry et al., 2003), had diminished ethanol sensitivity during the first few minutes of drug exposure (Figure 5A, Supplemental Figure S6A; #, Bonferroni multiple comparison, t(7)=2.91–4.92, p<0.05) and a trend toward blunted acute tolerance to ethanol at later time-points (Figure 5A). In contrast, worms carrying the exl-1(ok857) mutation, also likely a null allele (Berry & Hobert, 2006), had wild-type initial sensitivity to ethanol followed by significantly enhanced acute functional ethanol tolerance (Figure 5A; †, Bonferroni multiple comparison; t(7)=2.91–4.92, p<0.05). Importantly, while internal ethanol concentrations increased with the duration of ethanol exposure as expected, neither mutation significantly altered internal tissue concentrations of ethanol determined at key time-points of behavioral testing as compared to N2 control animals (Figure 5B; two-way ANOVA; duration, (F(2,60)=29.19, p<0.0001); genotype (F(3,60)=3.07, p=0.0439; interaction between duration and genotype, (F(3,60)=0.1143, p=0.951, n.s.; Bonferroni multiple comparisons between N2 and other genotypes, t(11)=0.0824–1.94, p>0.05, n.s., n=6). The behavioral consequences of exc-4 and exl-1 mutations are therefore likely to be
