After 9 generations of selection for high DID, the HDID-1 mice were tested in a standard DID test, except they were offered two bottles, one containing water and one containing alcohol. They drank more alcohol than controls (and, in fact, nearly the amount they usually drank in a single-bottle DID test), but they also drank some water, and their BECs were significantly lower (Crabbe et al. 2009). We have not yet tested the HDID-2 line for two-bottle DID, or for intoxication after drinking. Because selection is unidirectional, we are dependent upon finding differences between the HDID lines and the non-selected control for concluding that there are correlated response differences for a given trait. Control line values can differ considerably depending on the phenotype, and genetic confounds due to accidental fixation of genes in the control lines can lead to false positive or false negative conclusions. One advantage of finding that the HDID-2 line is showing increasing BECs at nearly exactly the same rate as the HDID-1 line is that we can perform correlated response tests using all three lines simultaneously, while predicting the rank order of differences among lines (HDID-1 ≥ HDID-2 > Control, for example).
