Addiction to alcohol, opiates, and stimulant drugs involves both changes in attention–decision making and increased temporal lobe anxiety–negative affect urgency. Addiction-induced negative affect and depression-like behaviors also are linked to neuroimmune signaling because neuroimmune signals can alter moods. For example, a compound called lipopolysaccharide (LPS) that can induce brain innate immune genes causes depression-like behavior that mimics components of addiction-like negative affect. LPS naturally binds with one of the TLRs (i.e., TLR4) and this interaction results in NF-κB activation, ultimately leading to the induction of innate immune genes. In humans, LPS infusions reduce reward responses and increase depressed mood (Eisenberger et al. 2010). Likewise, when patients with cancer or viral infections are treated with agents such as interferon and IL that influence innate immune genes, they may experience severe depression as a major adverse effect (Kelley and Dantzer 2011). Innate immune activators such as LPS, chemokines, and cytokines can mimic the amplification of depressed mood that occurs during repeated cycles of drug abuse or stress (Breese et al. 2008). All of these observations further support the link between neuroimmune signaling
