Cited by 499Cannabis and Cannabinoid ResearchStress Responses and CortisolNeuropeptides and Animal Physiology

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Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal

Rodrı́guez de Fonseca, Fernando, Carrera, M. Rocı́o A., Navarro, Miguel, Koob, George F., Weiss, Friedbert·1997·Science

DOI 10.1126/science.276.5321.2050

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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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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
ORCID: Navarro, Miguel
Koob, George F.
Weiss, Friedbert
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1997-06-27
Volume: 276
Issue: 5321
Pages: 2050-2054
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.276.5321.2050
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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Activation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal

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