Year: 2011
Type: article
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.
Source: Frontiers in Psychiatry
Authors: Fulton T. Crews, Ryan Peter Vetreno
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: MOLECULAR AND CELLULAR PATHOGENESIS IN ALCOHOLISM, UNC-CH NADIA Scientific Core, 5/8 NADIA U01 Effects of Adolescent Alcohol on adult brain Neurocircuitry, G3338828332, Adult neurobiology following adolescent drinking, 1/1 NADIA U24 Administrative Core, 2/2 Mechanisms of alcohol pathology: A collaborative partnership between NCCU & UNC, G9000102076, G9000148061, Molecular and Circuit Pathogenesis of Alcohol Use Disorders, Brain Tissue Resource Center for Alcohol Research, Molecular and Cellular Alcohol Research Training
OpenAlex ID: W2056709697