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CRF–CRF 1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats
Open accessAbstract
Nicotine, the main psychoactive ingredient of tobacco, induces negative emotional symptoms during abstinence that contribute to a profound craving for nicotine. However, the neurobiological mechanisms underlying how nicotine produces dependence remains poorly understood. We demonstrate one mechanism for both the anxiety-like symptoms of withdrawal and excessive nicotine intake observed after abstinence, through recruitment of the extrahypothalamic stress peptide corticotropin-releasing factor (CRF) system and activation of CRF 1 receptors. Overactivation of the CRF–CRF 1 system may contribute to nicotine dependence and may represent a prominent target for investigating the vulnerability to tobacco addiction.
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“Nicotine withdrawal leads to an increase in CRF in the CeA, and blockade of CRF1 receptors diminishes nicotine withdrawalinduced anxiety-like behavior (George et al. 2007).”
From Nicotine Withdrawal (2015) · cites this paper as George et al. 2007
In the citing paper
“CRF levels increase by >500% in the CeA after nicotine withdrawal is precipitated with the nAChR antagonist mecamylamine [158].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [158]
In the citing paper
“Injection of a CRF1 receptor antagonist into the CeA blunts anxiety-like behavior during nicotine withdrawal [158].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [158]
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Metadata
- Authors
- George, O., Ghozland, S., Azar, M. R., Cottone, P., Zorrilla, E. P., Parsons, L. H., O'Dell, L. E., Richardson, H. N., & Koob, G. F.
- Affiliations
- Scripps Research Institute (US)
- Department of Psychology, University of Texas, El Paso, TX 79968
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-10-23
- Volume
- 104
- Issue
- 43
- Pages
- 17198-17203
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2040467
- OpenAlex
- W2097077325
- Cited by
- 245
- References
- 45
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 4 · 2021: 11 · 2020: 9 · 2019: 17 · 2018: 17 · 2017: 11 · 2016: 14 · 2015: 14 · 2014: 16 · 2013: 22 · 2012: 16
- FWCI
- 12.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Robert Wood Johnson Foundation
- Tobacco-Related Disease Research Program (12RT-0099)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, P01DK026741)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- nicotine dependence, nicotine self-administration, nicotine withdrawal, corticotropin-releasing factor, CRF1 receptor, anxiety-like behavior, tobacco dependence, nicotine craving
- MeSH terms
- CRF Receptor, Type 1, Amygdala, Animals, Anxiety, Behavior, Animal, Corticotropin-Releasing Hormone, Feeding Behavior, Male, Mecamylamine, Nicotine, Self Administration, Substance Withdrawal Syndrome, Behavior, Addictive, Rats, Wistar, Receptors, Corticotropin-Releasing Hormone, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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