Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels

Detalhes bibliográficos
Autor(a) principal: Sales, Amanda J.
Data de Publicação: 2018
Outros Autores: Crestani, Carlos C. [UNESP], Guimarães, Francisco S., Joca, Sâmia R.L.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.pnpbp.2018.06.002
http://hdl.handle.net/11449/171118
Resumo: Cannabidiol (CBD) is a compound of Cannabis sativa with relevant therapeutic potential in several neuropsychiatric disorders including depression. CBD treatment has shown significant antidepressant-like effects in different rodent preclinical models. However, the mechanisms involved in CBD-induced antidepressant effects are still poorly understood. Therefore, this work aimed at investigating the participation of serotonin (5-HT) and/or noradrenaline (NA) in CBD-induced antidepressant-like effects in the forced swimming test (FST) by: 1) testing if CBD co-administration with serotonergic (fluoxetine, FLX) or noradrenergic (desipramine, DES) antidepressants would have synergistic effects; and 2) investigating if 5-HT or NA depletion would impair CBD-induced behavioral effects. Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST. Ineffective doses of CBD (7 mg/kg), when co-administered with ineffective doses of FLX (5 mg/kg) or DES (2.5 mg/kg) resulted in significant antidepressant-like effects, thus implicating synergistic and/or additive mechanisms. Pretreatment with PCPA (an inhibitor of serotonin synthesis: 150 mg/kg, i.p., once per day for 4 days), but not DSP-4 (a noradrenergic neurotoxin: 1 μg/μl, i.c.v., 24 h before the test), reduced monoamine levels in the brain. However, only PCPA treatment abolished CBD-induced behavioral effects in FST, indicating the participation of serotonergic mechanisms. None of the treatments induced locomotor effects. Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS).
id UNSP_15b155cf62f1fb078ca8bfe55d1e197f
oai_identifier_str oai:repositorio.unesp.br:11449/171118
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levelsAntidepressantCannabidiolDesipramineFluoxetineNoradrenalineSerotoninCannabidiol (CBD) is a compound of Cannabis sativa with relevant therapeutic potential in several neuropsychiatric disorders including depression. CBD treatment has shown significant antidepressant-like effects in different rodent preclinical models. However, the mechanisms involved in CBD-induced antidepressant effects are still poorly understood. Therefore, this work aimed at investigating the participation of serotonin (5-HT) and/or noradrenaline (NA) in CBD-induced antidepressant-like effects in the forced swimming test (FST) by: 1) testing if CBD co-administration with serotonergic (fluoxetine, FLX) or noradrenergic (desipramine, DES) antidepressants would have synergistic effects; and 2) investigating if 5-HT or NA depletion would impair CBD-induced behavioral effects. Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST. Ineffective doses of CBD (7 mg/kg), when co-administered with ineffective doses of FLX (5 mg/kg) or DES (2.5 mg/kg) resulted in significant antidepressant-like effects, thus implicating synergistic and/or additive mechanisms. Pretreatment with PCPA (an inhibitor of serotonin synthesis: 150 mg/kg, i.p., once per day for 4 days), but not DSP-4 (a noradrenergic neurotoxin: 1 μg/μl, i.c.v., 24 h before the test), reduced monoamine levels in the brain. However, only PCPA treatment abolished CBD-induced behavioral effects in FST, indicating the participation of serotonergic mechanisms. None of the treatments induced locomotor effects. Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS).Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Pharmacology School of Medicine of Ribeirão Preto University of São PauloLaboratory of Pharmacology School of Pharmaceutical Sciences of Araraquara São Paulo State University (UNESP)Center for Interdisciplinary Research on Applied Neurosciences (NAPNA) University of São PauloDepartment of Physics and Chemistry School of Pharmaceutical Sciences of Ribeirão Preto University of São PauloTranslational Neuropsychiatry Unit Department of Clinical Medicine Aarhus UniversityLaboratory of Pharmacology School of Pharmaceutical Sciences of Araraquara São Paulo State University (UNESP)FAPESP: 2015/01955-0; 2012/17626CNPq: 465458/2014-9CNPq: INCT-CNPqUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Aarhus UniversitySales, Amanda J.Crestani, Carlos C. [UNESP]Guimarães, Francisco S.Joca, Sâmia R.L.2018-12-11T16:53:58Z2018-12-11T16:53:58Z2018-08-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article255-261application/pdfhttp://dx.doi.org/10.1016/j.pnpbp.2018.06.002Progress in Neuro-Psychopharmacology and Biological Psychiatry, v. 86, p. 255-261.1878-42160278-5846http://hdl.handle.net/11449/17111810.1016/j.pnpbp.2018.06.0022-s2.0-850487312332-s2.0-85048731233.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengProgress in Neuro-Psychopharmacology and Biological Psychiatry1,714info:eu-repo/semantics/openAccess2023-11-16T06:14:08Zoai:repositorio.unesp.br:11449/171118Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T17:52:39.145984Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
title Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
spellingShingle Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
Sales, Amanda J.
Antidepressant
Cannabidiol
Desipramine
Fluoxetine
Noradrenaline
Serotonin
title_short Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
title_full Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
title_fullStr Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
title_full_unstemmed Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
title_sort Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
author Sales, Amanda J.
author_facet Sales, Amanda J.
Crestani, Carlos C. [UNESP]
Guimarães, Francisco S.
Joca, Sâmia R.L.
author_role author
author2 Crestani, Carlos C. [UNESP]
Guimarães, Francisco S.
Joca, Sâmia R.L.
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Estadual Paulista (Unesp)
Aarhus University
dc.contributor.author.fl_str_mv Sales, Amanda J.
Crestani, Carlos C. [UNESP]
Guimarães, Francisco S.
Joca, Sâmia R.L.
dc.subject.por.fl_str_mv Antidepressant
Cannabidiol
Desipramine
Fluoxetine
Noradrenaline
Serotonin
topic Antidepressant
Cannabidiol
Desipramine
Fluoxetine
Noradrenaline
Serotonin
description Cannabidiol (CBD) is a compound of Cannabis sativa with relevant therapeutic potential in several neuropsychiatric disorders including depression. CBD treatment has shown significant antidepressant-like effects in different rodent preclinical models. However, the mechanisms involved in CBD-induced antidepressant effects are still poorly understood. Therefore, this work aimed at investigating the participation of serotonin (5-HT) and/or noradrenaline (NA) in CBD-induced antidepressant-like effects in the forced swimming test (FST) by: 1) testing if CBD co-administration with serotonergic (fluoxetine, FLX) or noradrenergic (desipramine, DES) antidepressants would have synergistic effects; and 2) investigating if 5-HT or NA depletion would impair CBD-induced behavioral effects. Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST. Ineffective doses of CBD (7 mg/kg), when co-administered with ineffective doses of FLX (5 mg/kg) or DES (2.5 mg/kg) resulted in significant antidepressant-like effects, thus implicating synergistic and/or additive mechanisms. Pretreatment with PCPA (an inhibitor of serotonin synthesis: 150 mg/kg, i.p., once per day for 4 days), but not DSP-4 (a noradrenergic neurotoxin: 1 μg/μl, i.c.v., 24 h before the test), reduced monoamine levels in the brain. However, only PCPA treatment abolished CBD-induced behavioral effects in FST, indicating the participation of serotonergic mechanisms. None of the treatments induced locomotor effects. Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS).
publishDate 2018
dc.date.none.fl_str_mv 2018-12-11T16:53:58Z
2018-12-11T16:53:58Z
2018-08-30
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.pnpbp.2018.06.002
Progress in Neuro-Psychopharmacology and Biological Psychiatry, v. 86, p. 255-261.
1878-4216
0278-5846
http://hdl.handle.net/11449/171118
10.1016/j.pnpbp.2018.06.002
2-s2.0-85048731233
2-s2.0-85048731233.pdf
url http://dx.doi.org/10.1016/j.pnpbp.2018.06.002
http://hdl.handle.net/11449/171118
identifier_str_mv Progress in Neuro-Psychopharmacology and Biological Psychiatry, v. 86, p. 255-261.
1878-4216
0278-5846
10.1016/j.pnpbp.2018.06.002
2-s2.0-85048731233
2-s2.0-85048731233.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Progress in Neuro-Psychopharmacology and Biological Psychiatry
1,714
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 255-261
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808128869576736768