Cited by 313Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersNeurotransmitter Receptor Influence on Behavior

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Induction of innate immune genes in brain create the neurobiology of addiction

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Crews, F.T., Zou, Jian, Qin, Liya·2011·Brain, Behavior, and Immunity

DOI 10.1016/j.bbi.2011.03.003PMC PMC3552373

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Abstract

Addiction occurs through repeated abuse of drugs that progressively reduce behavioral control and cognitive flexibility while increasing limbic negative emotion. Recent discoveries indicate neuroimmune signaling underlies addiction and co-morbid depression. Low threshold microglia undergo progressive stages of innate immune activation involving astrocytes and neurons with repeated drug abuse, stress, and/or cell damage signals. Increased brain NF-κB transcription of proinflammatory chemokines, cytokines, oxidases, proteases, TLR and other genes create loops amplifying NF-κB transcription and innate immune target gene expression. Human post-mortem alcoholic brain has increased NF-κB and NF-κB target gene message, increased microglial markers and chemokine-MCP1. Polymorphisms of human NF-κB1 and other innate immune genes contribute to genetic risk for alcoholism. Animal transgenic and genetic studies link NF-κB innate immune gene expression to alcohol drinking. Human drug addicts show deficits in behavioral flexibility modeled pre-clinically using reversal learning. Binge alcohol, chronic cocaine, and lesions link addiction neurobiology to frontal cortex, neuroimmune signaling and loss of behavioral flexibility. Addiction also involves increasing limbic negative emotion and depression-like behavior that is reflected in hippocampal neurogenesis. Innate immune activation parallels loss of neurogenesis and increased depression-like behavior. Protection against loss of neurogenesis and negative affect by anti-oxidant, anti-inflammatory, anti-depressant, opiate antagonist and abstinence from ethanol dependence link limbic affect to changes in innate immune signaling. The hypothesis that innate immune gene induction underlies addiction and affective disorders creates new targets for therapy.

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Authors: Crews, F. T., Zou, J., & Qin, L.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Crews, F.T.
ORCID: Crews, F.T.
Zou, Jian
Qin, Liya
Venue: Brain, Behavior, and Immunity
Publisher: Elsevier BV
Published: 2011-06
Volume: 25
Pages: S4-S12
ISSN: 0889-1591 (ISSN-L)
DOI: 10.1016/j.bbi.2011.03.003
PMC: PMC3552373
OpenAlex: W2018062658
Cited by: 313
References: 105
Citations by year: 2026: 7 · 2025: 14 · 2024: 21 · 2023: 13 · 2022: 17 · 2021: 25 · 2020: 21 · 2019: 18 · 2018: 15 · 2017: 25 · 2016: 23 · 2015: 28 · 2014: 33 · 2013: 18 · 2012: 28
FWCI: 2.41
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Brain Behavior and Immunity (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
UNC Libraries
Funders: Center for Alcohol Studies
National Institutes of Health (AA-11605, AA019767)
National Institute on Alcohol Abuse and Alcoholism (P50AA011605, AA 11605, U24AA020022, U01AA020023, AA020023, AA020022, AA020024, U24AA020024, U54AA019767, AA019767, P60AA011605)
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: addiction, neuroimmune signaling, innate immunity, NF-κB, microglia, astrocytes, alcoholism, cocaine dependence, behavioral flexibility, reversal learning, depression-like behavior, hippocampal neurogenesis, MCP-1, chemokines, cytokines, genetic polymorphism, frontal cortex, anti-inflammatory therapy
MeSH terms: Brain, Humans, Neuroimmunomodulation, Behavior, Addictive, Substance-Related Disorders

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Induction of innate immune genes in brain create the neurobiology of addiction

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