Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-Possible involvement of 5-HT1A and CB1 receptors
Abstract
RATIONALE: Systemic administration of cannabidiol (CBD), the main non-psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects. The mechanism of action of CBD is thought to involve the activation of 5-HT1A receptors and the modulation of endocannabinoid levels with subsequent CB1 activation. The brain regions involved in CBD-induced antidepressant-like effects remain unknown. The ventral medial prefrontal cortex (vmPFC), which includes the infralimbic (IL) and prelimbic (PL) subregions, receives dense serotonergic innervation and plays a significant role in stress responses. OBJECTIVE: To test the hypothesis that the administration of CBD into the IL or PL would induce an antidepressant-like effect through 5-HT1A and CB1 activation. METHODS: Rats received intra-IL or -PL microinjections of CBD (10-60 nmol/side), 8-OH-DPAT (5-HT1A agonist, 5-10 nmol/side), anandamide (AEA, 0.5 pmol/side) or vehicle (0.2 μl/side) and were submitted to the forced swimming (FST) or to the open field (OFT) tests. Independent CBD-treated groups were pre-treated with WAY100635 (10, 30 nmol/side, 5-HT1A antagonist) or AM251 (10 pmol/side, CB1 antagonist) and submitted to the same tests. An additional group was treated with WAY100635 followed by anandamide. RESULTS: CBD (PL: 10-60 nmol; IL:45-60 nmol) and 8-OH-DPAT (10 nmol) administration significantly reduced the immobility time in the FST, without changing locomotor activity in the OFT. WAY100635 (30 nmol) did not induce effect per se but blocked CBD, 8-OH-DPAT and AEA effects. Additionally, AM251 blocked CBD-effects. CONCLUSION: administration of CBD into the vmPFC induces antidepressant-like effects possibly through indirect activation of CB1 and 5-HT1A receptors.
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CBD has antidepressant-like effects observed in the forced swimming stress, Wistar-Kyoto and bulbectomy models.
“These effects could be associated with the antidepressant-like effects of CBD observed in the forced swimming stress, (33, 34), Wistar-Kyoto (35) and bulbectomy models (36).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [34]
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Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age
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- Authors
- Sartim, A. G., Guimarães, F. S., & Joca, S. R. L.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Joca, S.R.L.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 303
- Pages
- 218-227
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2303387325
- Cited by
- 156
- References
- 64
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 13 · 2023: 15 · 2022: 21 · 2021: 24 · 2020: 10 · 2019: 22 · 2018: 18 · 2017: 10 · 2016: 5
- FWCI
- 14.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (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 › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Keywords
- cannabidiol, antidepressant-like effects, ventromedial prefrontal cortex, infralimbic cortex, prelimbic cortex, 5-HT1A receptor, CB1 receptor, endocannabinoid system, anandamide, 8-OH-DPAT, forced swim test, depression, microinjection
- MeSH terms
- Animals, Antidepressive Agents, Arachidonic Acids, Behavior, Animal, Cannabidiol, Male, Motor Activity, Piperazines, Piperidines, Pyrazoles, Pyridines, Serotonin Antagonists, Rats, Wistar, 8-Hydroxy-2-(di-n-propylamino)tetralin, Prefrontal Cortex, Receptor, Cannabinoid, CB1, Receptor, Serotonin, 5-HT1A, Rats, Polyunsaturated Alkamides, Serotonin 5-HT1 Receptor Agonists, Endocannabinoids
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