drug-seeking behavior. To examine a gene by environment interaction, animals that have been genetically modified by “knocking in” human genes with different versions of a specific polymorphism or more generally “knocking out” the gene can be exposed to specific environmental variables (e.g., repeated exposure to a drug or drug cues). Key neuroanatomical loci and pathways in the rat include the VTA, nucleus accumbens, prefrontal cortex, dorsal striatum, and basolateral amygdala (see Kalivas & Volkow, 2005). Changes in the loci and pathways that result from the combination of the gene and the environmental exposure can be conceptualized as a GXE interaction.