TY - JOUR AU - Crews, Fulton AU - Vetreno, Ryan PY - 2011 M3 - Review TI - Addiction, Adolescence, and Innate Immune Gene Induction JO - Frontiers in Psychiatry UR - https://www.frontiersin.org/articles/10.3389/fpsyt.2011.00019 VL - 2 SN - 1664-0640 N2 - Repeated drug use/abuse amplifies psychopathology, progressively reducing frontal lobe behavioral control, and cognitive flexibility while simultaneously increasing limbic temporal lobe negative emotionality. The period of adolescence is a neurodevelopmental stage characterized by poor behavioral control as well as strong limbic reward and thrill seeking. Repeated drug abuse and/or stress during this stage increase the risk of addiction and elevate activator innate immune signaling in the brain. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a key glial transcription factor that regulates proinflammatory chemokines, cytokines, oxidases, proteases, and other innate immune genes. Induction of innate brain immune gene expression (e.g., NF-κB) facilitates negative affect, depression-like behaviors, and inhibits hippocampal neurogenesis. In addition, innate immune gene induction alters cortical neurotransmission consistent with loss of behavioral control. Studies with anti-oxidant, anti-inflammatory, and anti-depressant drugs as well as opiate antagonists link persistent innate immune gene expression to key behavioral components of addiction, e.g., negative affect-anxiety and loss of frontal–cortical behavioral control. This review suggests that persistent and progressive changes in innate immune gene expression contribute to the development of addiction. Innate immune genes may represent a novel new target for addiction therapy. ER -