The DOI matches its Crossref record; 105 of the 105 references it cites were found in a registry or an index.
Induction of innate immune genes in brain create the neurobiology of addiction
Open accessAbstract
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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“Accumulating evidence suggests a close link between drug abuse and neuroinflammation (Crews et al., 2011; Clark et al., 2013).”
From Engineered Extracellular Vesicles Loaded With miR-124 Attenuate Cocaine-Mediated Activation of Microglia (2020) · cites this paper as Crews et al., 2011
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“Our pathway analysis results are consistent with earlier findings showing induction of innate immune genes by stress and drug abuse35.”
From Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism (2019) · cites this paper as [35]
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Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants
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Activators and target genes of Rel/NF-κB transcription factors
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Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration
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Self-citationHippocampal volume and depression: a meta-analysis of MRI studies
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Adolescent cortical development: A critical period of vulnerability for addiction
Crews, F., He, J., & Hodge, C. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2006.12.001 · Cited by 1,091
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Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K. D., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.052 · Cited by 1,748
Gene Coexpression Networks in Human Brain Identify Epigenetic Modifications in Alcohol Dependence
Ponomarev, I., Wang, S., Zhang, L., Harris, R. A., & Mayfield, R. D. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3136-11.2012 · Cited by 387
Common cellular and molecular mechanisms in obesity and drug addiction
Kenny, P. J. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3105 · Cited by 382
Alcohol dependence as a chronic pain disorder
Egli, M., Koob, G. F., & Edwards, S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.07.010 · Cited by 347
Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior
Crews, F. T., Vetreno, R. P., Broadwater, M., & Robinson, D. L. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.012138 · Cited by 356
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Metadata
- Authors
- Crews, F. T., Zou, J., & Qin, L.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Crews, F.T.
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 25
- Pages
- S4-S12
- ISSN
- 0889-1591 (ISSN-L)
- 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
- 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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