Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice.
The anxiolytic and antidepressant properties of cannabidiol (CBD) have been evaluated in several studies. However, the molecular mechanisms involved in these actions remain unclear. A total of 130 male mice were used. CBD's ability to modulate emotional disturbances (anxiety and depressive-like beha...
| Authors: | ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2022 |
| Country: | España |
| Institution: | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| Repository: | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| OAI Identifier: | oai:isabial.fundanetsuite.com:p8681 |
| Online Access: | https://isabial.portalinvestigacion.com/publicaciones8681 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027088/ |
| Access Level: | Open access |
| Keyword: | G-protein-coupled receptor 55 GABA(A) receptor anxiety cannabidiol cannabinoid receptor 1 cannabinoid receptor 2 depression |
| _version_ | 1878736255409192960 |
|---|---|
| author | Austrich-Olivares A |
| author2 | García-Gutiérrez MS Illescas L Gasparyan A Manzanares J |
| author2_role | author author author author |
| author_browse | Austrich-Olivares A García-Gutiérrez MS Gasparyan A Illescas L Manzanares J |
| author_facet | Austrich-Olivares A García-Gutiérrez MS Illescas L Gasparyan A Manzanares J |
| author_role | author |
| collection | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| description | The anxiolytic and antidepressant properties of cannabidiol (CBD) have been evaluated in several studies. However, the molecular mechanisms involved in these actions remain unclear. A total of 130 male mice were used. CBD's ability to modulate emotional disturbances (anxiety and depressive-like behaviors) was evaluated at different doses in wild-type (CD1; 10, 20 and 30 mg/kg; i.p.) and knockout (CB1KO, CB2KO; GPR55KO; 20 mg/kg) mice. Moreover, CBD effects (20 mg/kg; i.p.) were evaluated in mice previously treated with the CB1r-antagonist SR141716A (2mg/kg; i.p.). Relative gene expression analyses of Cnr1 and Cnr2, Gpr55 and GABA(A)a2 and ?2 receptor subunits were performed in the amygdala (AMY) and hippocampus (HIPP) of CD1 mice. CBD (10 and 20 mg/kg) showed anxiolytic and antidepressant actions in CD1 mice, being more effective at 20 mg/kg. Its administration did not induce anxiolytic actions in CB1KO mice, contrary to CB2KO and GPR55KO. In all of them, the lack of cannabinoid receptors did not modify the antidepressant activity of CBD. Interestingly, the administration of the CB1r antagonist SR141716A blocked the anxiolytic-like activity of CBD. Real-time PCR studies revealed a significant reduction in Cnr1 and GABA(A)a2 and ?2 gene expression in the HIPP and AMY of CD1 mice treated with CBD. Opposite changes were observed in the Cnr2. Indeed, Gpr55 was increased in the AMY and reduced in the HIPP. CB1r appears to play a relevant role in modulating the anxiolytic actions of CBD. Moreover, this study revealed that CBD also modified the gene expression of GABA(A) subunits a2 and ?2 and CB1r, CB2r and GPR55, in a dose- and brain-region-dependent manner, supporting a multimodal mechanism of action for CBD. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_8bd368730e00d4e030d5e7b0083f9779 |
| institution | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| instname_str | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:isabial.fundanetsuite.com:p8681 |
| publishDate | 2022 |
| publishDateSort | 2022 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| spelling | Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. Austrich-Olivares A García-Gutiérrez MS Illescas L Gasparyan A Manzanares J G-protein-coupled receptor 55 GABA(A) receptor anxiety cannabidiol cannabinoid receptor 1 cannabinoid receptor 2 depression The anxiolytic and antidepressant properties of cannabidiol (CBD) have been evaluated in several studies. However, the molecular mechanisms involved in these actions remain unclear. A total of 130 male mice were used. CBD's ability to modulate emotional disturbances (anxiety and depressive-like behaviors) was evaluated at different doses in wild-type (CD1; 10, 20 and 30 mg/kg; i.p.) and knockout (CB1KO, CB2KO; GPR55KO; 20 mg/kg) mice. Moreover, CBD effects (20 mg/kg; i.p.) were evaluated in mice previously treated with the CB1r-antagonist SR141716A (2mg/kg; i.p.). Relative gene expression analyses of Cnr1 and Cnr2, Gpr55 and GABA(A)a2 and ?2 receptor subunits were performed in the amygdala (AMY) and hippocampus (HIPP) of CD1 mice. CBD (10 and 20 mg/kg) showed anxiolytic and antidepressant actions in CD1 mice, being more effective at 20 mg/kg. Its administration did not induce anxiolytic actions in CB1KO mice, contrary to CB2KO and GPR55KO. In all of them, the lack of cannabinoid receptors did not modify the antidepressant activity of CBD. Interestingly, the administration of the CB1r antagonist SR141716A blocked the anxiolytic-like activity of CBD. Real-time PCR studies revealed a significant reduction in Cnr1 and GABA(A)a2 and ?2 gene expression in the HIPP and AMY of CD1 mice treated with CBD. Opposite changes were observed in the Cnr2. Indeed, Gpr55 was increased in the AMY and reduced in the HIPP. CB1r appears to play a relevant role in modulating the anxiolytic actions of CBD. Moreover, this study revealed that CBD also modified the gene expression of GABA(A) subunits a2 and ?2 and CB1r, CB2r and GPR55, in a dose- and brain-region-dependent manner, supporting a multimodal mechanism of action for CBD. MDPI https://isabial.portalinvestigacion.com/publicaciones8681 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027088/ |
| spellingShingle | Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. Austrich-Olivares A G-protein-coupled receptor 55 GABA(A) receptor anxiety cannabidiol cannabinoid receptor 1 cannabinoid receptor 2 depression |
| status_str | publishedVersion |
| title | Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. |
| title_full | Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. |
| title_fullStr | Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. |
| title_full_unstemmed | Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. |
| title_short | Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. |
| title_sort | Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice. |
| topic | G-protein-coupled receptor 55 GABA(A) receptor anxiety cannabidiol cannabinoid receptor 1 cannabinoid receptor 2 depression |
| topic_facet | G-protein-coupled receptor 55 GABA(A) receptor anxiety cannabidiol cannabinoid receptor 1 cannabinoid receptor 2 depression |
| url | https://isabial.portalinvestigacion.com/publicaciones8681 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027088/ |