- PMID: 36768376
- DOI: 10.3390/ijms24032052
Cannabidiol (CBD) is a potential antidepressant agent. We examined the association between the antidepressant effects of CBD and alterations in brain microRNAs in the unpredictable chronic mild stress (UCMS) model for depression. UCMS male rats were injected with vehicle or CBD (10 mg/kg) and tested for immobility time in the forced swim test. Alterations in miRNAs (miR16, miR124, miR135a) and genes that encode for the 5HT1a receptor, the serotonergic transporter SERT, β-catenin, and CB1 were examined. UCMS increased immobility time in a forced swim test (i.e., depressive-like behavior) and altered the expression of miRNAs and mRNA in the ventromedial prefrontal cortex (vmPFC), raphe nucleus, and nucleus accumbens. Importantly, CBD restored UCMS-induced upregulation in miR-16 and miR-135 in the vmPFC as well as the increase in immobility time. CBD also restored the UCMS-induced decrease in htr1a, the gene that encodes for the serotonergic 5HT1a receptor; using a pharmacological approach, we found that the 5HT1a receptor antagonist WAY100135 blocked the antidepressant-like effect of CBD on immobility time. Our findings suggest that the antidepressant effects of CBD in a rat model for depression are associated with alterations in miR-16 and miR-135 in the vmPFC and are mediated by the 5HT1a receptor.
Keywords: 5-HT1a receptor, CB1 receptor, cannabidiol, depression, microRNAs, prefrontal cortex
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Cannabidiol in the prelimbic cortex modulates the comorbid condition between the chronic neuropathic pain and depression-like behaviour in rats: The role of medial prefrontal cortex 5-HT1A and CB1 receptors.Brain Res Bull. 2021 Sep;174:323-338. doi: 10.1016/j.brainresbull.2021.06.017. Epub 2021 Jun 27.PMID: 34192579
Cannabidiol induces antidepressant and anxiolytic-like effects in experimental type-1 diabetic animals by multiple sites of action.Metab Brain Dis. 2021 Apr;36(4):639-652. doi: 10.1007/s11011-020-00667-3. Epub 2021 Jan 19.PMID: 33464458
Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3364-78. doi: 10.1098/rstb.2011.0389.PMID: 23108553 Free PMC article. Review.
Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: involvement of 5HT1A receptors and previous stressful experience.Eur Neuropsychopharmacol. 2014 Mar;24(3):410-9. doi: 10.1016/j.euroneuro.2013.10.012. Epub 2013 Oct 31.PMID: 24321837
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