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Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects
Open accessAbstract
The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, G(i/o) proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.
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“This is unlikely, however, as we observed no significant difference in the number of rats climbing (41, 42) among HU210-, AM281-, and vehicle-treated groups in the first 5 minutes of the pretest sessions of the FST.”
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Metadata
- Authors
- Jiang, W.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-11-01
- Volume
- 115
- Issue
- 11
- Pages
- 3104-3116
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1253627
- OpenAlex
- W2097448914
- Cited by
- 527
- References
- 62
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 18 · 2023: 17 · 2022: 16 · 2021: 30 · 2020: 24 · 2019: 23 · 2018: 19 · 2017: 18 · 2016: 19 · 2015: 27 · 2014: 39 · 2013: 33 · 2012: 33
- FWCI
- 20.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Journal of Clinical Investigation (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Saskatchewan Health Research Foundation
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cannabinoids, HU-210, CB1 receptor, adult hippocampal neurogenesis, dentate gyrus, neural stem/progenitor cells, anxiolytic effects, antidepressant-like effects, ERK signaling, G protein signaling
- MeSH terms
- Animals, Antidepressive Agents, Arachidonic Acids, Cannabinoids, Cells, Cultured, Hippocampus, Male, Neurons, Rats, Inbred F344, Stem Cells, Dronabinol, Anti-Anxiety Agents, Signal Transduction, Rats, Wistar, Rats, Long-Evans, Receptor, Cannabinoid, CB1, Cell Proliferation, Rats, Polyunsaturated Alkamides, Endocannabinoids
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