The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake
The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adu...
| Autores: | ; ; |
|---|---|
| Tipo de documento: | Artigo |
| Estado: | Accepted version |
| Data de publicação: | 2020 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/44465 |
| Acesso em linha: | http://hdl.handle.net/10230/44465 http://dx.doi.org/10.1111/adb.12778 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | Cannabidiol Cocaine Neurogenesis Reinforcement Self-administration Temozolomide |
| _version_ | 1878731767634984960 |
|---|---|
| author | Luján Pérez, Miguel Ángel, 1991- |
| author2 | Cantacorps Centellas, Lídia, 1991- Valverde Granados, Olga |
| author2_role | author author |
| author_browse | Cantacorps Centellas, Lídia, 1991- Luján Pérez, Miguel Ángel, 1991- Valverde Granados, Olga |
| author_facet | Luján Pérez, Miguel Ángel, 1991- Cantacorps Centellas, Lídia, 1991- Valverde Granados, Olga |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice. Cocaine intake was modelled using the intravenous cocaine self-administration procedure in CD1 male mice. Cannabidiol (20 mg/kg) reduced cocaine self-administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis. Our results show that a 6-day repeated temozolomide treatment (25 mg/kg/day), a chemotherapy drug that blocks hippocampal neurogenesis, prevented cannabidiol-induced increment in the early stages of neuronal maturation and differentiation, without altering the basal levels of BrdU/NeuN and doublecortin immunostaining. The reduction of total cocaine intake and operant behaviour acquisition observed following cannabidiol exposure was attenuated by temozolomide treatment. Our results also show a similar effect of temozolamide on a cannabidiol-induced improvement of novel object recognition memory, a task influenced by the proneurogenic effects of cannabidiol (10 and 20 mg/kg). The anxiolytic effects of cannabidiol (10 and 20 mg/kg), however, remained unaffected after its proneurogenic effects decreased. The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice. Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_362d171f4e785aa4a0b45bc33b2abb8a |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10230/44465 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | Wiley-Blackwell |
| publisherStr | Wiley-Blackwell |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake Luján Pérez, Miguel Ángel, 1991- Cantacorps Centellas, Lídia, 1991- Valverde Granados, Olga Cannabidiol Cocaine Neurogenesis Reinforcement Self-administration Temozolomide The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice. Cocaine intake was modelled using the intravenous cocaine self-administration procedure in CD1 male mice. Cannabidiol (20 mg/kg) reduced cocaine self-administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis. Our results show that a 6-day repeated temozolomide treatment (25 mg/kg/day), a chemotherapy drug that blocks hippocampal neurogenesis, prevented cannabidiol-induced increment in the early stages of neuronal maturation and differentiation, without altering the basal levels of BrdU/NeuN and doublecortin immunostaining. The reduction of total cocaine intake and operant behaviour acquisition observed following cannabidiol exposure was attenuated by temozolomide treatment. Our results also show a similar effect of temozolamide on a cannabidiol-induced improvement of novel object recognition memory, a task influenced by the proneurogenic effects of cannabidiol (10 and 20 mg/kg). The anxiolytic effects of cannabidiol (10 and 20 mg/kg), however, remained unaffected after its proneurogenic effects decreased. The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice. Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders. This work was supported by Ministerio de Economía y Competitividad (grant number SAF2016-75966-R-FEDER), by the European Union's Horizon 2020 research andinnovation programme 2014–2020 under grant agreement no 634143. M.A.L. received FPU grant (15/02492) from the Ministeriode Educacion, Cultura y Deporte. L.C.received FPI grant(BES-2014-070657) from the Ministerio de Economía y Competitividad.The Department of Experimental and Health Sciences (UPF) is an“Unidad de Excelencia María de Maeztu” funded by the MINECO (Ref. MDM-2014-0370).The authors thank Gerald-Patrick Fannon for his English proofreading and editing of the manuscript, and Phytoplant Research S.L. for providing CBD compound.The authors declare no conflicts of interest. AUTHORS CONTRIBUTION M.A.L. and O.V. were responsible for the study concept and design.M.A.L .and L.C carried out the experimental studies. M.A.L. and O.V.drafted the manuscript and editing of the manuscript, and Phytoplant Research S.L. for providing CBD compound.The authors declare no conflicts of interest. Wiley-Blackwell http://hdl.handle.net/10230/44465 http://dx.doi.org/10.1111/adb.12778 |
| spellingShingle | The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake Luján Pérez, Miguel Ángel, 1991- Cannabidiol Cocaine Neurogenesis Reinforcement Self-administration Temozolomide |
| status_str | acceptedVersion |
| title | The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake |
| title_full | The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake |
| title_fullStr | The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake |
| title_full_unstemmed | The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake |
| title_short | The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake |
| title_sort | The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake |
| topic | Cannabidiol Cocaine Neurogenesis Reinforcement Self-administration Temozolomide |
| topic_facet | Cannabidiol Cocaine Neurogenesis Reinforcement Self-administration Temozolomide |
| url | http://hdl.handle.net/10230/44465 http://dx.doi.org/10.1111/adb.12778 |