Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice

Background: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeat...

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Autores: Gomes, Felipe V., Issy, Ana Carolina, Ferreira, Frederico R., Viveros, María Paz, Del Bel, Elaine A., Guimarães, Francisco S.
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/23324
Acceso en línea:https://hdl.handle.net/20.500.14352/23324
Access Level:acceso abierto
Palabra clave:615.9
591.18
Antipsychotic
Cannabidiol
Cannabinoid
Clozapine
NMDA receptor hypofunction
Schizophrenia
Fisiología animal (Biología)
Neurociencias (Biológicas)
Farmacología (Farmacia)
2401.13 Fisiología Animal
2490 Neurociencias
3209 Farmacología
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oai_identifier_str oai:docta.ucm.es:20.500.14352/23324
network_acronym_str ES
network_name_str España
repository_id_str
spelling Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in MiceGomes, Felipe V.Issy, Ana CarolinaFerreira, Frederico R.Viveros, María PazDel Bel, Elaine A.Guimarães, Francisco S.615.9591.18AntipsychoticCannabidiolCannabinoidClozapineNMDA receptor hypofunctionSchizophreniaFisiología animal (Biología)Neurociencias (Biológicas)Farmacología (Farmacia)2401.13 Fisiología Animal2490 Neurociencias3209 FarmacologíaBackground: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Methods: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calciumbinding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Results: MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by itself did not induce any effect. Moreover, CBD effects were similar to those induced by repeated clozapine treatment.Oxford University PressUniversidad Complutense de Madrid20152015-01-2420152015-01-24journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/23324reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial 3.0 Españahttps://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/233242026-06-02T12:44:21Z
dc.title.none.fl_str_mv Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice
title Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice
spellingShingle Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice
Gomes, Felipe V.
615.9
591.18
Antipsychotic
Cannabidiol
Cannabinoid
Clozapine
NMDA receptor hypofunction
Schizophrenia
Fisiología animal (Biología)
Neurociencias (Biológicas)
Farmacología (Farmacia)
2401.13 Fisiología Animal
2490 Neurociencias
3209 Farmacología
title_short Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice
title_full Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice
title_fullStr Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice
title_full_unstemmed Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice
title_sort Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice
dc.creator.none.fl_str_mv Gomes, Felipe V.
Issy, Ana Carolina
Ferreira, Frederico R.
Viveros, María Paz
Del Bel, Elaine A.
Guimarães, Francisco S.
author Gomes, Felipe V.
author_facet Gomes, Felipe V.
Issy, Ana Carolina
Ferreira, Frederico R.
Viveros, María Paz
Del Bel, Elaine A.
Guimarães, Francisco S.
author_role author
author2 Issy, Ana Carolina
Ferreira, Frederico R.
Viveros, María Paz
Del Bel, Elaine A.
Guimarães, Francisco S.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 615.9
591.18
Antipsychotic
Cannabidiol
Cannabinoid
Clozapine
NMDA receptor hypofunction
Schizophrenia
Fisiología animal (Biología)
Neurociencias (Biológicas)
Farmacología (Farmacia)
2401.13 Fisiología Animal
2490 Neurociencias
3209 Farmacología
topic 615.9
591.18
Antipsychotic
Cannabidiol
Cannabinoid
Clozapine
NMDA receptor hypofunction
Schizophrenia
Fisiología animal (Biología)
Neurociencias (Biológicas)
Farmacología (Farmacia)
2401.13 Fisiología Animal
2490 Neurociencias
3209 Farmacología
description Background: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Methods: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calciumbinding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Results: MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by itself did not induce any effect. Moreover, CBD effects were similar to those induced by repeated clozapine treatment.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-24
2015
2015-01-24
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/23324
url https://hdl.handle.net/20.500.14352/23324
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial 3.0 España
https://creativecommons.org/licenses/by-nc/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial 3.0 España
https://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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