Cited by 156Cannabis and Cannabinoid ResearchTreatment of Major DepressionMedicinal Plant Extracts Effects

Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-Possible involvement of 5-HT1A and CB1 receptors

Sartim, A.G., Guimarães, F.S., Joca, S.R.L.·2016·Behavioural Brain Research

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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Crossref · 10.1016/j.bbr.2016.01.033

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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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