Cannabidiol attenuates sensorimotor gating disruption and molecular changes induced by chronic antagonism of NMDA receptors in mice
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BACKGROUND: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. METHODS: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calcium-binding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. RESULTS: MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by itself did not induce any effect. Moreover, CBD effects were similar to those induced by repeated clozapine treatment. CONCLUSIONS: These results indicate that repeated treatment with CBD, similar to clozapine, reverses the psychotomimetic-like effects and attenuates molecular changes observed after chronic administration of an NMDAR antagonist. These data support the view that CBD may have antipsychotic properties.
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CBD, as well as clozapine, prevented the decrease in parvalbumin expression and the increase in FosB/ΔFosB expression in the mPFC after chronic injection of MK-801.
“In respect to the implication of the mPFC in CBD's antipsychotic action, we showed that CBD, as well as the atypical antipsychotic clozapine, prevented the decrease in the expression of parvalbumin (a calcium-binding protein expressed in a subset of GABAergic interneurons) and the increase in FosB/ΔFosB expression in the mPFC after chronic injection of the NMDA antagonist MK-801 (70).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [70]
Chronic CBD administration (for 21 days) decreased social impairment and memory deficits induced by repeated administration of MK801.
“In the former study, CBD was administered chronically (for 21 days) and was also able to decrease the social impairment and memory deficits induced by the repeated administration of MK801 (70).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [70]
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- Authors
- Gomes, F. V., Issy, A. C., Ferreira, F. R., Viveros, M.-P., Del Bel, E. A., & Guimarães, F. S.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Corresponding author
- Gomes, Felipe V.
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-01-24
- Volume
- 18
- Issue
- 5
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC4376539
- OpenAlex
- W2165640020
- Cited by
- 89
- References
- 78
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 8 · 2023: 6 · 2022: 7 · 2021: 13 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 12 · 2016: 7 · 2015: 4
- FWCI
- 6.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Library Open Repository (Universidad Complutense Madrid) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- 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 › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cannabidiol, sensorimotor gating, prepulse inhibition, NMDA receptor antagonism, MK-801, animal models of schizophrenia, antipsychotic effects, FosB/ΔFosB, parvalbumin, GABAergic interneurons, GluN1 subunit, medial prefrontal cortex, hippocampus, clozapine
- MeSH terms
- Animals, Behavior, Animal, Cannabidiol, Disease Models, Animal, Dose-Response Relationship, Drug, Hippocampus, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Parvalbumins, RNA, Messenger, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Proto-Oncogene Proteins c-fos, Treatment Outcome, Prefrontal Cortex, Mice, Sensory Gating, GABAergic Neurons, Prepulse Inhibition
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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