Extension of GXE research to animal models is important scientifically because research in humans (with few, but important exceptions discussed below under Human Laboratory Models) is almost exclusively correlational and, thus, incapable of providing strong inferences concerning causation. In humans, additionally, the same environmental exposures that are most plausible candidates for interacting with individual gene effects on risk are also likely to be correlated with genetic risk. For example, alcohol risk genes as well as risky environments are passed down from parents to offspring living in the household: these are the conditions under which the dissection of GXE effects, for a variety of technical reasons, is most challenging (e.g. Purcell, 2002; Rathouz et al, 2008). Animal models provide opportunities for control of both genetic factors and environmental exposures, opportunities to observe the temporal sequencing and unfolding of behaviors and the processes presumably mediating them, and opportunities to conduct analyses across multiple levels of biological organization (e.g., neurocircuitry, cellular, genetic and epigenetic) that involve high levels of invasiveness. As noted in a recent Institute of Medicine (IOM; 2006) report, rodent models
