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Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression
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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953518/ https://www.ncbi.nlm.nih.gov/pubmed/36768376 http://dx.doi.org/10.3390/ijms24032052 |
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author | Bright, Uri Akirav, Irit |
author_facet | Bright, Uri Akirav, Irit |
author_sort | Bright, Uri |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9953518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99535182023-02-25 Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression Bright, Uri Akirav, Irit Int J Mol Sci Article 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. MDPI 2023-01-20 /pmc/articles/PMC9953518/ /pubmed/36768376 http://dx.doi.org/10.3390/ijms24032052 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bright, Uri Akirav, Irit Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression |
title | Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression |
title_full | Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression |
title_fullStr | Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression |
title_full_unstemmed | Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression |
title_short | Cannabidiol Modulates Alterations in PFC microRNAs in a Rat Model of Depression |
title_sort | cannabidiol modulates alterations in pfc micrornas in a rat model of depression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953518/ https://www.ncbi.nlm.nih.gov/pubmed/36768376 http://dx.doi.org/10.3390/ijms24032052 |
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