There is strong evidence, especially in mouse populations derived from the C57BL/6J (B6) and DBA/2J (D2) inbred strains, for a negative genetic relationship between ethanol consumption (two-bottle choice, continuous access) and both acute and chronic ethanol withdrawal (see Metten et al. 1998a). High ethanol withdrawal (scored as handling-induced convulsions [HICs]) is associated with low ethanol consumption and vice versa. Data supporting this relationship have been obtained in the BXD recombinant inbred (RI) panel, B6×D2 F2 intercrosses, two independent selections from B6×D2 F2 intercrosses, and in a BXD F1 (RIX) population. Putative reciprocal quantitative trait loci (QTLs), which appear to contribute to the negative correlation, are found on chromosomes (Chr) 1 (distal), 2 (mid), 4 (mid), and 15 (proximal; Metten et al. 1998a). Reciprocal QTLs are defined by alleles associated with high withdrawal/low consumption and vice versa. To date, the genes within the reciprocal QTL intervals that are driving the differential responses (the quantitative trait genes [QTGs]) have not been determined.
