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Front Psychiatry. 2011 Apr 27;2:19. doi: 10.3389/fpsyt.2011.00019. eCollection 2011.

Addiction, adolescence, and innate immune gene induction.

Author information

  • 1Department of Pharmacology, Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill Chapel Hill, NC, USA.

Abstract

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

PMID:
21629837
[PubMed]
PMCID:
PMC3098669
Free PMC Article

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