Addiction, adolescence, and innate immune gene induction
- 1 Department of Pharmacology, Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- 2 Department of Psychiatry, Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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.
Keywords: addiction, alcoholism, chemokines, microglia, neurogenesis
Citation: Crews FT and Vetreno RP (2011) Addiction, adolescence, and innate immune gene induction. Front. Psychiatry 2:19. doi: 10.3389/fpsyt.2011.00019
Received: 10 March 2011; Paper pending published: 27 March 2011;
Accepted: 11 April 2011; Published online: 27 April 2011.
, University of North Carolina at Chapel Hill, USA
Copyright: © 2011 Crews and Vetreno. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.
*Correspondence: Fulton T. Crews, Bowles Center for Alcohol Studies, The School of Medicine, The University of North Carolina at Chapel Hill, CB #7178, 1021 Thurston-Bowles Building, Chapel Hill, NC 27599-71780, USA. e-mail: firstname.lastname@example.org