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Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal
Abstract
Corticotropin-releasing factor (CRF) has been implicated in the mediation of the stress-like and negative affective consequences of withdrawal from drugs of abuse, such as alcohol, cocaine, and opiates. This study sought to determine whether brain CRF systems also have a role in cannabinoid dependence. Rats were treated daily for 2 weeks with the potent synthetic cannabinoid HU-210. Withdrawal, induced by the cannabinoid antagonist SR 141716A, was accompanied by a marked elevation in extracellular CRF concentration and a distinct pattern of Fos activation in the central nucleus of the amygdala. Maximal increases in CRF corresponded to the time when behavioral signs resulting from cannabinoid withdrawal were at a maximum. These data suggest that long-term cannabinoid administration alters CRF function in the limbic system of the brain, in a manner similar to that observed with other drugs of abuse, and also induces neuroadaptive processes that may result in future vulnerability to drug dependence.
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“CRF production in, and release from, the amygdala is greatly potentiated during withdrawal from a variety of drugs of abuse, as well as during chronic stress (Merlo Pich et al 1995; Rodriguez de Fonseca et al 1997; Richter and Weiss 1999; Stout et al 2000; Zorrilla et al 2001; Olive et al 2002; Funk et al 2006; George et al 2007).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Rodriguez de Fonseca et al 1997
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Metadata
- Authors
- Rodrı́guez de Fonseca, F., Carrera, M. R. A., Navarro, M., Koob, G. F., & Weiss, F.
- Affiliations
- F. Rodrı́guez de Fonseca and M. Navarro, Instituto Complutense de Drogodependencias, Departamento de Psicobiologı́a, Facultad de Psicologı́a, Universidad Complutense de Madrid, 28223 Madrid, Spain.
- Universidad Complutense de Madrid (ES)
- Corresponding author
- Navarro, Miguel
- Venue
- Science
- Published
- 1997-06-27
- Volume
- 276
- Issue
- 5321
- Pages
- 2050-2054
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2124997151
- Cited by
- 499
- References
- 45
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 3 · 2019: 11 · 2018: 19 · 2017: 7 · 2016: 7 · 2015: 7 · 2014: 8 · 2013: 12 · 2012: 21
- FWCI
- 27.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r03da008426-02)
- National Institute on Drug Abuse (DA 08426)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, P01DK026741)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- corticotropin-releasing factor, cannabinoid withdrawal, HU-210, SR141716A, Fos activation, central amygdala, limbic system, neural adaptation, drug addiction, stress response
- MeSH terms
- Rimonabant, Amygdala, Animals, Anxiety, Behavior, Animal, Brain, Corticosterone, Corticotropin-Releasing Hormone, Male, Piperidines, Pyrazoles, Receptors, Drug, Substance Withdrawal Syndrome, Dronabinol, Proto-Oncogene Proteins c-fos, Rats, Wistar, Microdialysis, Receptors, Cannabinoid, Rats
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