Anxiety and the bad feelings of negative affect are associated with increased drug craving as a key component of addiction (Breese et al. 2005; Koob and Volkow 2010). Breese' laboratory models addiction with repeated cycles of ethanol consumption and/or stress that progressively amplify anxiety and negative affect consistent with the cycles of stress and drug abuse known to promote addiction. Interestingly, brain injections of innate immune inducing molecules, e.g. the chemokine MCP-1, the cytokine TNFα, or the TLR4 agonist, lipopolysaccaride an innate immune inducer, progressively increase addiction-like anxiety substituting for an episode of stress or drug abuse (Breese et al. 2008). Cycles of stress and/or drug abuse cause progressive addiction-like anxiety and are known to induce innate immune genes in brain. The discovery that innate immune molecules injected into brain substitute for stress and/or drug abuse cycles promoting addiction-like anxiety, supports the role innate immune genes in driving the neurocircuitry and neurobiology that result in addiction-like behavior.