Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats

Campos, Alline Cristina; Guimarães, Francisco Silveira

doi:10.1007/s00213-008-1168-x

Cited by 364Cannabis and Cannabinoid ResearchMedicinal Plant Extracts EffectsNeurotransmitter Receptor Influence on Behavior

Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats

Campos, Alline Cristina, Guimarães, Francisco Silveira·2008·Psychopharmacology

DOI 10.1007/s00213-008-1168-x

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Abstract

Rationale Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that induces anxiolytic effects. However, the brain sites and mechanisms of these effects remain poorly understood. The dorsolateral periaqueductal gray (dlPAG) is a midbrain structure related to anxiety that contains receptors proposed to interact with CBD such as 5HT1A. In addition, since CBD has been shown to inhibit anandamide metabolism, CB1 receptors could also be involved in the effects of this cannabinoid.Objectives To investigate if the dlPAG could be a possible site of the anxiolytic effects induced by CBD and if these effects depend on CB1 or 5HT1A receptors.Materials and methods Male Wistar rats with cannulae aimed at the dlPAG were tested in the elevated plus maze (EPM) and the Vogel conflict test (VCT).Results CBD injected into the dlPAG produced anxiolytic-like effects in the EPM with a bell-shaped dose-response curve. The anxiolytic effect of CBD was confirmed in the VCT. These effects were prevented by WAY100635, a 5HT1A receptor antagonist, but not by AM251, an antagonist of CB1 receptors.Conclusion These results suggest the CBD interacts with 5HT1A receptors to produce anxiolytic effects in the dlPAG.

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CBD injected into the dorsolateral periaqueductal gray of rats produced anxiolytic-like effects in the elevated plus-maze and elevated T-maze.
“Additionally, CBD injected into the dorsolateral periaqueductal gray of rats produced anxiolytic-like effects in the elevated plus-maze and elevated T-maze, and these effects were prevented by a 5HT1A receptor antagonist (Soares et al, 2010; Campos and Guimaraes, 2008).”
From Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients (2011) · cites this paper as Campos and Guimaraes, 2008
These anxiolytic-like effects were prevented by a 5HT1A receptor antagonist.
“Additionally, CBD injected into the dorsolateral periaqueductal gray of rats produced anxiolytic-like effects in the elevated plus-maze and elevated T-maze, and these effects were prevented by a 5HT1A receptor antagonist (Soares et al, 2010; Campos and Guimaraes, 2008).”
From Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients (2011) · cites this paper as Campos and Guimaraes, 2008
CBD induced acute anxiolytic effects when injected into the dPAG and BNST.
“As shown in Figure 2, CBD induced acute anxiolytic effects when injected into the dPAG and BNST (21, 37–41).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [37]

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Authors: Campos, A. C., & Guimarães, F. S.
Affiliations: Universidade de São Paulo (BR)
Corresponding author: Guimarães, Francisco Silveira
ORCID: Campos, Alline Cristina
Guimarães, Francisco Silveira
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2008-05-01
Volume: 199
Issue: 2
Pages: 223-230
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-008-1168-x
OpenAlex: W1987998857
Cited by: 364
References: 47
Citations by year: 2026: 14 · 2025: 15 · 2024: 24 · 2023: 23 · 2022: 27 · 2021: 37 · 2020: 41 · 2019: 25 · 2018: 18 · 2017: 19 · 2016: 14 · 2015: 13 · 2014: 12 · 2013: 14 · 2012: 24
FWCI: 10.04
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Topics: Health Sciences › Medicine › Pharmacology › 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, 5-HT1A receptor, anxiolytic effects, dorsolateral periaqueductal gray, CB1 receptor, anxiety, WAY-100635, AM251, elevated plus maze, Vogel conflict test
MeSH terms: Animals, Cannabidiol, Dose-Response Relationship, Drug, Male, Microinjections, Periaqueductal Gray, Piperazines, Piperidines, Pyrazoles, Pyridines, Serotonin Antagonists, Anti-Anxiety Agents, Rats, Wistar, Receptor, Cannabinoid, CB1, Receptor, Serotonin, 5-HT1A, Rats

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Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats

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