Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol

Gomes, Felipe V.; Llorente, Ricardo; Del Bel, Elaine A.; Viveros, Maria-Paz; López-Gallardo, Meritxell; Guimarães, Francisco S.

doi:10.1016/j.schres.2015.01.015

Cited by 147Cannabis and Cannabinoid ResearchSchizophrenia research and treatmentTryptophan and brain disorders

Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol

Gomes, Felipe V., Llorente, Ricardo, Del Bel, Elaine A., Viveros, Maria-Paz, López-Gallardo, Meritxell, Guimarães, Francisco S.·2015·Schizophrenia Research

DOI 10.1016/j.schres.2015.01.015

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Abstract

NMDA receptor hypofunction could be involved, in addition to the positive, also to the negative symptoms and cognitive deficits found in schizophrenia patients. An increasing number of data has linked schizophrenia with neuroinflammatory conditions and glial cells, such as microglia and astrocytes, have been related to the pathogenesis of schizophrenia. Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa with anti-inflammatory and neuroprotective properties induces antipsychotic-like effects. The present study evaluated if repeated treatment with CBD (30 and 60 mg/kg) would attenuate the behavioral and glial changes observed in an animal model of schizophrenia based on the NMDA receptor hypofunction (chronic administration of MK-801, an NMDA receptor antagonist, for 28 days). The behavioral alterations were evaluated in the social interaction and novel object recognition (NOR) tests. These tests have been widely used to study changes related to negative symptoms and cognitive deficits of schizophrenia, respectively. We also evaluated changes in NeuN (a neuronal marker), Iba-1 (a microglia marker) and GFAP (an astrocyte marker) expression in the medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens core and shell, and dorsal hippocampus by immunohistochemistry. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Repeated MK-801 administration impaired performance in the social interaction and NOR tests. It also increased the number of GFAP-positive astrocytes in the mPFC and the percentage of Iba-1-positive microglia cells with a reactive phenotype in the mPFC and dorsal hippocampus without changing the number of Iba-1-positive cells. No change in the number of NeuN-positive cells was observed. Both the behavioral disruptions and the changes in expression of glial markers induced by MK-801 treatment were attenuated by repeated treatment with CBD or clozapine. These data reinforces the proposal that CBD may induce antipsychotic-like effects. Although the possible mechanism of action of these effects is still unknown, it may involve CBD anti-inflammatory and neuroprotective properties. Furthermore, our data support the view that inhibition of microglial activation may improve schizophrenia symptoms.

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Both CBD and clozapine prevented the increase in the number of GFAP-positive astrocytes in the mPFC and in the percentage of Iba-1-positive microglia cells with a reactive phenotype in the dorsal hippocampus and mPFC after repeated administration of MK-801.
“Finally, both CBD and clozapine prevented the increase in the number of GFAP-positive astrocytes in the mPFC and in the percentage of Iba-1-positive microglia cells with a reactive phenotype in the dorsal hippocampus and mPFCafter repeated administration of MK-801 (71).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [71]
CBD blocked PPI impairment induced by amphetamine after direct injection into the nucleus accumbens.
“Confirming the involvement of limbic sites in its antipsychotic effects, CBD blocked PPI impairment induced by amphetamine after direct injection into the nucleus accumbens (71).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [71]

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Authors: Gomes, F. V., Llorente, R., Del Bel, E. A., Viveros, M.-P., López-Gallardo, M., & Guimarães, F. S.
Affiliations: Universidade de São Paulo (BR)
Universidad Complutense de Madrid (ES)
ORCID: Gomes, Felipe V.
Llorente, Ricardo
Guimarães, Francisco S.
Venue: Schizophrenia Research
Publisher: Elsevier BV
Published: 2015-05
Volume: 164
Issue: 1-3
Pages: 155-163
ISSN: 0920-9964 (ISSN-L)
DOI: 10.1016/j.schres.2015.01.015
OpenAlex: W2028951205
Cited by: 147
References: 72
Citations by year: 2026: 4 · 2025: 13 · 2024: 15 · 2023: 8 · 2022: 13 · 2021: 24 · 2020: 11 · 2019: 14 · 2018: 15 · 2017: 14 · 2016: 12 · 2015: 4
FWCI: 10.86
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Schizophrenia Research (publishedVersion)
PubMed (publishedVersion)
Library Open Repository (Universidad Complutense Madrid) (submittedVersion)
Funders: FAPESP (012/17626-7)
CNPq (470311/2012-6)
Instituto de Salud Carlos III, Redes temáticas de Investigación Cooperativa en salud (RD2012/0028/0021)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: cannabidiol, schizophrenia
MeSH terms: Animals, Brain, Calcium-Binding Proteins, Cannabidiol, Clozapine, Disease Models, Animal, Dose-Response Relationship, Drug, Exploratory Behavior, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Male, Mice, Inbred C57BL, Microfilament Proteins, Neuroglia, Phosphopyruvate Hydratase, Psychotic Disorders, Antipsychotic Agents, Dizocilpine Maleate, Excitatory Amino Acid Antagonists, Maze Learning, Recognition, Psychology, Mice

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Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol

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