Our results clearly show that inflammatory activation (treatment with LPS) can produce long-lasting (up to 3 months, including several periods of alcohol deprivation) increases of ethanol intake, although there are differences in the size and persistence of the effect among different genetic backgrounds and between male and female mice. Both B6 and FVBxB6F1 mice showed the increased consumption. It should be noted that B6 show the highest level of ethanol preference and intake among all available inbred mouse strains (Belknap et al., 1993) and that the FVBxB6F1 show the highest alcohol intake of any mouse line (Blednov et al., 2005b). Thus, it is notable that even a single injection of LPS was able to produce a long-lasting increase in consumption in these high-drinking mice. This is consistent with our finding of reduced alcohol consumption in null mutant mice lacking key components of immune signaling (Blednov et al., 2005a, in press). These studies showed that mice lacking several chemokines and cytokines showed decreased alcohol consumption in the two-bottle choice test.