The volatile anesthetics (VAs) halothane and isoflurane completely disrupt coordinated movement, mating, and chemotaxis behaviors in C. elegans at concentrations similar to those required to produce unconsciousness in vertebrates. We have previously reported (PNAS, in press) the mapping of several genetic loci whose natural variation in recombinant inbred strains (RIs) produces a greater than 10-fold range in halothane potency. Here, we address if the potency of other VAs and nervous system depressants is controlled by the same or different loci. RIs derived from N2 and BO were scored for VA-induced uncoordination and ethanol immobilization (n=31). Halothane(n=55) and isoflurane(n=47) potencies for uncoordination were determined by the ability of adult worms to disperse in 45 min into a ring of OP50 at edge of a 9.5 cm plate. Ethanol potencies were scored by giving 20 - 100 animals in varying concentrations of ethanol a movement score of 2 (rapidly thrashing), 1 (slowly moving), or 0 (not moving). One way ANOVA was performed to determine linkage of loci to TC1 markers. Significance threshold was set at 0.05 by empirically determining the likelihood of a given F-ratio by 999 permutations of the phenotypes. The halothane and isoflurane EC50s were highly correlated in the 47 RIs common to the two datasets (r=0.72, p < 10^-8). However, the correlation of ethanol immobilization with either of the two anesthetic traits was poor (r halothane=0.18, p=0.45, r isoflurane=0.27, p=0.17).The correlation of ethanol immobilization with halothane-induced immobilization, which occurs at 10-fold higher VA concentrations, was also low at 0.18, p=0.34. Only one significant locus for isoflurane potency was found, and it mapped to chromosome V at the same location as the largest QTL for halothane potency near
stp18. Although highly heritable (H^2 = 88%), ethanol potency mapped to only one interaction QTL (p < 0.0009) between the center of chromosome V (
stP23) and the far right of the X chromosome (
stP2). Halothane and isoflurane action appears to be influenced by similar genetic determinants in these strains; ethanol action is controlled through a distinct genetic architecture.