The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: Involvement of 5HT1A receptors and previous stressful experience
Abstract
The prelimbic medial prefrontal cortex (PL) is an important encephalic structure involved in the expression of emotional states. In a previous study, intra-PL injection of cannabidiol (CBD), a major non-psychotomimetic cannabinoid present in the Cannabis sativa plant, reduced the expression of fear conditioning response. Although its mechanism remains unclear, CBD can facilitate 5HT1A receptor-mediated neurotransmission when injected into several brain structures. This study was aimed at verifying if intra-PL CBD could also induce anxiolytic-like effect in a conceptually distinct animal model, the elevated plus maze (EPM). We also verified if CBD effects in the EPM and contextual fear conditioning test (CFC) depend on 5HT1A receptors and previous stressful experience. CBD induced opposite effects in the CFC and EPM, being anxiolytic and anxiogenic, respectively. Both responses were prevented by WAY100,635, a 5HT1A receptor antagonist. In animals that had been previously (24h) submitted to a stressful event (2h-restraint) CBD caused an anxiolytic, rather than anxiogenic, effect in the EPM. This anxiolytic response was abolished by previous injection of metyrapone, a glucocorticoid synthesis blocker. Moreover, restraint stress increased 5HT1A receptors expression in the dorsal raphe nucleus, an effect that was attenuated by injection of metyrapone before the restraint procedure. Taken together, these results suggest that CBD modulation of anxiety in the PL depend on 5HT1A-mediated neurotransmission and previous stressful experience.
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“The anxiolytic-like effects produced by CBD injections into the rat infralimbic (Marinho et al., 2015) or prelimbic (Fogaca et al., 2014) cortices, BNST (Gomes et al., 2013; Gomes et al., 2012; Gomes et al., 2011) and dPAG (Campos et al., 2013a) are attenuated by concomitant 5-HT1A-R antagonism.”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Fogaca et al., 2014
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Cannabidiol as a Potential Treatment for Anxiety Disorders
Blessing, E., Steenkamp, M. M., Manzanares, J., & Marmar, C. R. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0387-1 · Cited by 752
Ligresti, A., PETROCELLIS, L. D., & Marzo, V. D. (2016) · Physiological Reviews · doi:10.1152/physrev.00002.2016 · Cited by 505
“Accordingly, CBD attenuates the acute autonomic responses associated to stress in rats by facilitating 5-HT1A receptor-mediated neurotrasmission (266, 724).”
BackgroundCannabidiol, neuroprotection and neuropsychiatric disorders
Campos, A. C., Fogaça, M. V., Sonego, A. B., & Guimarães, F. S. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.01.033 · Cited by 446
Self-citationMedial prefrontal cortex in neurological diseases
Xu, P., Chen, A., Li, Y., Xing, X., & Lü, H. (2019) · Physiological Genomics · doi:10.1152/physiolgenomics.00006.2019 · Cited by 360
Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age
Crippa, J. A., Guimarães, F. S., Campos, A. C., & Zuardi, A. W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02009 · Cited by 308
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Metadata
- Authors
- Fogaça, M. V., Reis, F. M. C. V., Campos, A. C., & Guimarães, F. S.
- Affiliations
- Universidade de São Paulo (BR)
- Universidade Federal de Minas Gerais (BR)
- Corresponding author
- Fogaça, M.V.
- Venue
- European Neuropsychopharmacology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 24
- Issue
- 3
- Pages
- 410-419
- ISSN
- 0924-977X (ISSN-L)
- OpenAlex
- W1975839888
- Semantic Scholar
- 520a9e101f0113f63d37c6bb694ef23f93512fe6
- Cited by
- 153
- References
- 52
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 12 · 2023: 10 · 2022: 12 · 2021: 24 · 2020: 16 · 2019: 16 · 2018: 10 · 2017: 17 · 2016: 12 · 2015: 9 · 2014: 2
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- cannabidiol, anxiety-like behavior, 5-HT1A receptor, restraint stress, anxiolytic effects, anxiogenic effects, dorsal raphe nucleus, metyrapone, glucocorticoid synthesis, WAY-100635, contextual fear conditioning, elevated plus maze
- MeSH terms
- Animals, Anxiety, Cannabidiol, Conditioning, Psychological, Dose-Response Relationship, Drug, Enzyme Inhibitors, Exploratory Behavior, Fear, Male, Metyrapone, Piperazines, Pyridines, Raphe Nuclei, Restraint, Physical, Stress, Psychological, Time Factors, Anti-Anxiety Agents, Rats, Wistar, Prefrontal Cortex, Maze Learning, Receptor, Serotonin, 5-HT1A, Serotonin 5-HT1 Receptor Antagonists
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