Functional interaction between opioid and cannabinoid receptors in drug self-administration.
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The present study was designed to explore the relationship between the cannabinoid and opioid receptors in animal models of opioid-induced reinforcement. The acute administration of SR141716A, a selective central cannabinoid CB1 receptor antagonist, blocked heroin self-administration in rats, as well as morphine-induced place preference and morphine self-administration in mice. Morphine-dependent animals injected with SR141716A exhibited a partial opiate-like withdrawal syndrome that had limited consequences on operant responses for food and induced place aversion. These effects were associated with morphine-induced changes in the expression of CB1 receptor mRNA in specific nuclei of the reward circuit, including dorsal caudate putamen, nucleus accumbens, and septum. Additionally, the opioid antagonist naloxone precipitated a mild cannabinoid-like withdrawal syndrome in cannabinoid-dependent rats and blocked cannabinoid self-administration in mice. Neither SR141716A nor naloxone produced any intrinsic effect on these behavioral models. The present results show the existence of a cross-interaction between opioid and cannabinoid systems in behavioral responses related to addiction and open new strategies for the treatment of opiate dependence.
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Antagonists of opioid receptors reduced discriminative stimulus and reinforcing effects produced by activation of CB1 receptors in preclinical studies.
“Evidence from pre-clinical studies demonstrates that antagonists of opioid receptors were able to reduce discriminative stimulus and reinforcing effects produced by the activation of CB1 receptors 71, 72.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [71]
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- Authors
- Navarro, M., Carrera, M. R. A., Fratta, W., Valverde, O., Cossu, G., Fattore, L., Chowen, J. A., Gómez, R., del Arco, I., Villanúa, M. A., Maldonado, R., Koob, G. F., & de Fonseca, F. R.
- Affiliations
- Scripps Research Institute (US)
- University of Cagliari (IT)
- Universitat Pompeu Fabra (ES)
- Consejo Superior de Investigaciones Científicas (ES)
- Universidad Complutense de Madrid (ES)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-07-15
- Volume
- 21
- Issue
- 14
- Pages
- 5344-5350
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762870
- OpenAlex
- W1699530412
- Cited by
- 378
- References
- 63
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 7 · 2023: 5 · 2022: 13 · 2021: 7 · 2020: 10 · 2019: 5 · 2018: 14 · 2017: 14 · 2016: 11 · 2015: 12 · 2014: 18 · 2013: 18 · 2012: 14
- FWCI
- 14.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Funders
- Sanofi
- Comunidad de Madrid
- Universidad Complutense de Madrid
- Consiglio Nazionale delle Ricerche
- National Institutes of Health
- Plan Nacional sobre Drogas
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741, P01DK026741)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- opioid-cannabinoid interaction, CB1 receptor, SR141716A, naloxone, heroin self-administration, morphine self-administration, place preference, opioid withdrawal, cannabinoid withdrawal, reward systems, nucleus accumbens, caudate-putamen, septum, addiction, opioid use disorder
- MeSH terms
- Rimonabant, Animals, Avoidance Learning, Cannabinoids, Caudate Nucleus, Conditioning, Operant, Heroin, Disease Models, Animal, Heroin Dependence, Male, Morphine, Morphine Dependence, Naloxone, Narcotic Antagonists, Nucleus Accumbens, Piperidines, Putamen, Pyrazoles, Receptors, Drug, Receptors, Opioid, RNA, Messenger, Self Administration, Rats, Wistar, Septum of Brain, Receptors, Cannabinoid, Mice, Rats
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