Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice
Abstract
Therapeutic effects of antidepressants and atypical antipsychotics may arise partially from their ability to stimulate neurogenesis. Cannabidiol (CBD), a phytocannabinoid present in Cannabis sativa, presents anxiolytic- and antipsychotic-like effects in preclinical and clinical settings. Anxiolytic-like effects of repeated CBD were shown in chronically stressed animals and these effects were parallel with increased hippocampal neurogenesis. However, antidepressant-like effects of repeated CBD administration in non-stressed animals have been scarcely reported. Here we investigated the behavioral consequences of single or repeated CBD administration in non-stressed animals. We also determined the effects of CBD on cell proliferation and neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ). Single CBD 3mg/kg administration resulted in anxiolytic-like effect in mice submitted to the elevated plus maze (EPM). In the tail suspension test (TST), single or repeated CBD administration reduced immobility time, an effect that was comparable to those of imipramine (20 mg/kg). Moreover, repeated CBD administration at a lower dose (3 mg/kg) increased cell proliferation and neurogenesis, as seen by an increased number of Ki-67-, BrdU- and doublecortin (DCX)-positive cells in both in DG and SVZ. Despite its antidepressant-like effects in the TST, repeated CBD administration at a higher dose (30 mg/kg) decreased cell proliferation and neurogenesis in the hippocampal DG and SVZ. Our findings show a dissociation between behavioral and proliferative effects of repeated CBD and suggest that the antidepressant-like effects of CBD may occur independently of adult neurogenesis in non-stressed Swiss mice.
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CBD increased stress-coping behaviors in a behavioral test largely used for screening antidepressant drugs.
“Recently, Schiavon et al. (106) showed that CBD increased stress-coping behaviors in a behavioral test largely used for the screening of antidepressant drugs”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [106]
CBD induces an increased number of Ki67, BrdU, and double cortin-positive cells in the hippocampus.
“suggested that CBD induces an increased the number of Ki67, BrdU, and double cortin-positive cells in the hippocampus.”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [106]
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- Authors
- Schiavon, A. P., Bonato, J. M., Milani, H., Guimarães, F. S., & Weffort de Oliveira, R. M.
- Affiliations
- Universidade Estadual de Maringá (BR)
- Universidade de São Paulo (BR)
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 64
- Pages
- 27-34
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W871462140
- Cited by
- 135
- References
- 77
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 7 · 2023: 14 · 2022: 14 · 2021: 29 · 2020: 10 · 2019: 14 · 2018: 15 · 2017: 10 · 2016: 7
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (47479820127)
- Universidade Estadual de Maringá
- Fundação Araucária
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Keywords
- cannabidiol, antidepressant-like effects, anxiolytic-like effects, adult neurogenesis, cell proliferation, dentate gyrus, subventricular zone, tail suspension test, elevated plus maze, dose-dependent effects, Ki-67, doublecortin, imipramine, phytocannabinoids
- MeSH terms
- Doublecortin Domain Proteins, Doublecortin Protein, Animals, Anxiety, Cannabidiol, Dose-Response Relationship, Drug, Emotions, Imipramine, Male, Microtubule-Associated Proteins, Motor Activity, Neuropeptides, Psychotropic Drugs, Random Allocation, Dentate Gyrus, Ki-67 Antigen, Cell Proliferation, Mice, Stem Cell Niche, Neurogenesis
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