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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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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