Cited by 153Cannabis and Cannabinoid ResearchMedicinal Plant Extracts EffectsNeurotransmitter Receptor Influence on Behavior

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Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: Involvement of 5HT1A receptors and previous stressful experience

Fogaça, M.V., Reis, F.M.C.V., Campos, A.C., Guimarães, F.S.·2014·European Neuropsychopharmacology

DOI 10.1016/j.euroneuro.2013.10.012

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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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Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585
Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat
Pellow, S., Chopin, P., File, S. E., & Briley, M. (1985) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(85)90031-7 · Cited by 5,822
Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide
Bisogno, T., Hanuš, L., PETROCELLIS, L. D., Tchilibon, S., Ponde, D. E., Brandi, I., Moriello, A. S., Davis, J. B., Mechoulam, R., & Marzo, V. D. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704327 · Cited by 1,315
The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress
Diorio, D., Viau, V, & Meaney, M. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-09-03839.1993 · Cited by 1,151
The neurobiology and control of anxious states
Millan, M. J. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00087-x · Cited by 978
Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb
Izzo, A. A., Borrelli, F., Capasso, R., Marzo, V. D., & Mechoulam, R. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.07.006 · Cited by 879
Agonistic properties of cannabidiol at 5-HT1a receptors
Russo, E. B., Burnett, A., Hall, B., & Parker, K. K. (2005) · Neurochemical Research · doi:10.1007/s11064-005-6978-1 · Cited by 878
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Radley, J. J., Rocher, A. B., Miller, M., Janssen, W. G. M., Liston, C., Hof, P. R., McEwen, B. S., & Morrison, J. H. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhi104 · Cited by 820
Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients
Bergamaschi, M. M., Queiroz, R. H. C., Chagas, M. H. N., de Oliveira, D. C. G., De Martinis, B. S., Kapczinski, F., Quevedo, J., Roesler, R., Schröder, N., Nardi, A. E., et al. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.6 · Cited by 771

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Background
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Raymundi, A. M., da Silva, T. R., Zampronio, A. R., Guimarães, F. S., Bertoglio, L. J., & Stern, C. A. J. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14895 · Cited by 39
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“However, in the prelimbic medial prefrontal cortex, CBD produced opposite effects in rats evaluated in the contextual fear conditioning paradigm and the EPM test, promoting anxiolytic- and anxiogenic- like effects respectively (Fogaca et al., 2014).”
BackgroundSelf-citation
Cannabinoid treatments for anxiety: A systematic review and consideration of the impact of sleep disturbance
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Influential
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“The dose of WAY 100635 was determined by previous published work by the principal investigators as well as Fogaca et al. (2014) and Rock et al. (2017).”
BackgroundMethod
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“It is an unavoidable and unconditioned aversiv situation that leads to HPA axis activation; cardiovascular responses; and behavioral changes, such as reduced exploration of open arms of the elevated plus-maze (EPM) (Busnardo et al., 2013; Choi et al., 2007; Dos Reis et al., 2014; Padovan and Guimaraes, 2000).”
Influential
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Cannabidiol Exposure During the Mouse Adolescent Period Is Without Harmful Behavioral Effects on Locomotor Activity, Anxiety, and Spatial Memory
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“These targets are found throughout the brain and in high density in the prefrontal cortex, hippocampus, striatum, and cerebellum (Fogaça et al., 2014; Warden et al., 2016; Ashton et al., 2017; Zuardi et al., 2017; Meyer et al., 2018; Barnes et al., 2020) and commonly affect intracellular calcium…”
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“Moreover, drugs with antagonistic actions at 5HT1A receptors have been reported to display anxiolytic effects [38].”
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“Fogaça et al. showed that CBD regulation of 5-HT 1A - mediated neurotransmission in the prelimbic medial prefrontal cortex influences anxiety [20].”
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“CBD directly injected into the PL or IL PFC before fear retrieval, decreased or increased contextual fear expression, respectively; both effects are mediated by the 5-HT1A receptor [231, 233].”
Self-citation
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“The anxiolytic effects of CBD (and CBDA) appear to be mediated by 5-HT1A receptor activation [22,23], unlike ∆9-THC, which modulates anxiety by CB1 receptor interaction [24].”
Background
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Cannabidiol impairs fear memory reconsolidation in female rats through dorsal hippocampus CB1 but not CB2 receptor interaction
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“Other proposed mechanisms include; agonism of TRP cation channels (De Petrocellis et al., 2012), the 5HT1-a receptor (Fogaça et al., 2014) and indirect modulation of the endocannabinoid system through blocking anandamide uptake and hydrolysis leading to an increase in CB1R activation (Sylantyev et…”
Background
Non-psychotropic phytocannabinoid interactions with voltage-gated sodium channels: An update on cannabidiol and cannabigerol
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“, 2019), 5-HT1A receptors (Campos and Guimarães, 2008; Fogaça et al., 2014; Marinho et al., 2015), and an inhibitor of adenosine reuptake by voltagedependent anion channel 1 (Rimmerman et al.”
Background
Cannabidiol prevents cognitive and social deficits in a male rat model of Alzheimer’s disease through CB1 activation and inflammation modulation
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The endocannabinoid system in social anxiety disorder: from pathophysiology to novel therapeutics
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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.
ORCID: Fogaça, M.V.
Reis, F.M.C.V.
Campos, A.C.
Guimarães, F.S.
Venue: European Neuropsychopharmacology
Publisher: Elsevier BV
Published: 2014-03
Volume: 24
Issue: 3
Pages: 410-419
ISSN: 0924-977X (ISSN-L)
DOI: 10.1016/j.euroneuro.2013.10.012
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: Involvement of 5HT1A receptors and previous stressful experience

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