The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats

Although the pharmacological and behavioural interactions between cocaine and alcohol are well established, less is known about how polyconsumption of these drugs affects the neurotransmitter systems involved in their psychoactive effects and in particular, in the process of addiction. Here, rats of...

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Autores: Marcos, Alberto, Ballesteros Yáñez, Inmaculada, Castillo Sarmiento, Carlos Alberto, Pardo, Felipe, Roura Martínez, David, Muñoz Rodríguez, José Ramón, Higueras Matas, Alejandro, Ambrosio, Emilio
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:dnet:ruidera_____::f089a8b3438338aee356c2205ab89623
Acceso en línea:https://doi.org/10.1016/j.neuropharm.2021.108937
https://www.sciencedirect.com/science/article/pii/S0028390821004949?__cf_chl_tk=oU8R5D4c_eh2weLl4v3FPBWII.GJT0HqtAO2kesPg0s-1777977691-1.0.1.1-YvP80SXtqsnELp0J6wt4BWNjczZR3mdrymrHSBxKwqI
https://hdl.handle.net/10578/48324
Access Level:acceso abierto
Palabra clave:Co-abuse
Cocaine
Ethanol
GABAergic
Glutamatergic and endocannabinoid systems
Mesocorticolimbic system
Rat
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spelling The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female ratsMarcos, AlbertoBallesteros Yáñez, InmaculadaCastillo Sarmiento, Carlos AlbertoPardo, FelipeRoura Martínez, DavidMuñoz Rodríguez, José RamónHigueras Matas, AlejandroAmbrosio, EmilioCo-abuseCocaineEthanolGABAergicGlutamatergic and endocannabinoid systemsMesocorticolimbic systemRatAlthough the pharmacological and behavioural interactions between cocaine and alcohol are well established, less is known about how polyconsumption of these drugs affects the neurotransmitter systems involved in their psychoactive effects and in particular, in the process of addiction. Here, rats of both sexes at two stages of development were studied under a chronic regime of intravenous cocaine and/or alcohol administration. Brain samples from the medial prefrontal cortex, nucleus accumbens, hippocampus and amygdala were extracted to analyse the mRNA expression of genes encoding subunits of the GABA, NMDA and AMPA receptors, as well as the expression of the CB1 receptor, and that of enzymes related to the biosynthesis and degradation of endocannabinoids. Moreover, two synaptic scaffold proteins related to GABA and NMDA receptors, gephyrin and PSD-95, were quantified in Western blots. Significant interactions between cocaine and alcohol were common, affecting the GABAergic and endocannabinoid systems in the medial prefrontal cortex and amygdala of young adults, whereas such interactions were evident in the glutamatergic and endocannabinoid systems in adults, as well as a more pronounced sex effect. Significant interactions between these drugs affecting the scaffold proteins were evident in the medial prefrontal cortex and nucleus accumbens of young adults, and in the nucleus accumbens and amygdala of adults, but not in the hippocampus. These results highlight the importance of considering the interactions between cocaine and alcohol on neurotransmitter systems in the context of polyconsumption, specifically when treating problems of abuse of these two substances.Elsevier202620262022info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://doi.org/10.1016/j.neuropharm.2021.108937https://www.sciencedirect.com/science/article/pii/S0028390821004949?__cf_chl_tk=oU8R5D4c_eh2weLl4v3FPBWII.GJT0HqtAO2kesPg0s-1777977691-1.0.1.1-YvP80SXtqsnELp0J6wt4BWNjczZR3mdrymrHSBxKwqIhttps://hdl.handle.net/10578/48324reponame:RUIdeRA. Repositorio Institucional de la UCLMinstname:Universidad de Castilla-La ManchaInglésEste trabajo fue apoyado por subvenciones del Ministerio de Sanidad, Servicios Sociales e Igualdad (Red de Trastornos Adictivos- Proyecto No.: RTA-RD16/0017/0022 del Instituto de Salud Carlos III- y Plan Nacional sobre Drogas, Proyecto No.: 2016I073); Ministerio de Ciencia e Innovación (Proyecto No.: PSI2016-80541-P ); UNED (Plan de Promoción de la Investigación) ; y Unión Europea (Proyecto No.: JUST/2013/DPIP/AG/4823-EU MADNESS).info:eu-repo/semantics/openAccessoai:dnet:ruidera_____::f089a8b3438338aee356c2205ab896232026-05-27T07:36:41Z
dc.title.none.fl_str_mv The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats
title The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats
spellingShingle The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats
Marcos, Alberto
Co-abuse
Cocaine
Ethanol
GABAergic
Glutamatergic and endocannabinoid systems
Mesocorticolimbic system
Rat
title_short The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats
title_full The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats
title_fullStr The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats
title_full_unstemmed The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats
title_sort The interactions of alcohol and cocaine regulate the expression of genes involved in the GABAergic, glutamatergic and endocannabinoid systems of male and female rats
dc.creator.none.fl_str_mv Marcos, Alberto
Ballesteros Yáñez, Inmaculada
Castillo Sarmiento, Carlos Alberto
Pardo, Felipe
Roura Martínez, David
Muñoz Rodríguez, José Ramón
Higueras Matas, Alejandro
Ambrosio, Emilio
author Marcos, Alberto
author_facet Marcos, Alberto
Ballesteros Yáñez, Inmaculada
Castillo Sarmiento, Carlos Alberto
Pardo, Felipe
Roura Martínez, David
Muñoz Rodríguez, José Ramón
Higueras Matas, Alejandro
Ambrosio, Emilio
author_role author
author2 Ballesteros Yáñez, Inmaculada
Castillo Sarmiento, Carlos Alberto
Pardo, Felipe
Roura Martínez, David
Muñoz Rodríguez, José Ramón
Higueras Matas, Alejandro
Ambrosio, Emilio
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Co-abuse
Cocaine
Ethanol
GABAergic
Glutamatergic and endocannabinoid systems
Mesocorticolimbic system
Rat
topic Co-abuse
Cocaine
Ethanol
GABAergic
Glutamatergic and endocannabinoid systems
Mesocorticolimbic system
Rat
description Although the pharmacological and behavioural interactions between cocaine and alcohol are well established, less is known about how polyconsumption of these drugs affects the neurotransmitter systems involved in their psychoactive effects and in particular, in the process of addiction. Here, rats of both sexes at two stages of development were studied under a chronic regime of intravenous cocaine and/or alcohol administration. Brain samples from the medial prefrontal cortex, nucleus accumbens, hippocampus and amygdala were extracted to analyse the mRNA expression of genes encoding subunits of the GABA, NMDA and AMPA receptors, as well as the expression of the CB1 receptor, and that of enzymes related to the biosynthesis and degradation of endocannabinoids. Moreover, two synaptic scaffold proteins related to GABA and NMDA receptors, gephyrin and PSD-95, were quantified in Western blots. Significant interactions between cocaine and alcohol were common, affecting the GABAergic and endocannabinoid systems in the medial prefrontal cortex and amygdala of young adults, whereas such interactions were evident in the glutamatergic and endocannabinoid systems in adults, as well as a more pronounced sex effect. Significant interactions between these drugs affecting the scaffold proteins were evident in the medial prefrontal cortex and nucleus accumbens of young adults, and in the nucleus accumbens and amygdala of adults, but not in the hippocampus. These results highlight the importance of considering the interactions between cocaine and alcohol on neurotransmitter systems in the context of polyconsumption, specifically when treating problems of abuse of these two substances.
publishDate 2022
dc.date.none.fl_str_mv 2022
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://doi.org/10.1016/j.neuropharm.2021.108937
https://www.sciencedirect.com/science/article/pii/S0028390821004949?__cf_chl_tk=oU8R5D4c_eh2weLl4v3FPBWII.GJT0HqtAO2kesPg0s-1777977691-1.0.1.1-YvP80SXtqsnELp0J6wt4BWNjczZR3mdrymrHSBxKwqI
https://hdl.handle.net/10578/48324
url https://doi.org/10.1016/j.neuropharm.2021.108937
https://www.sciencedirect.com/science/article/pii/S0028390821004949?__cf_chl_tk=oU8R5D4c_eh2weLl4v3FPBWII.GJT0HqtAO2kesPg0s-1777977691-1.0.1.1-YvP80SXtqsnELp0J6wt4BWNjczZR3mdrymrHSBxKwqI
https://hdl.handle.net/10578/48324
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Este trabajo fue apoyado por subvenciones del Ministerio de Sanidad, Servicios Sociales e Igualdad (Red de Trastornos Adictivos- Proyecto No.: RTA-RD16/0017/0022 del Instituto de Salud Carlos III- y Plan Nacional sobre Drogas, Proyecto No.: 2016I073); Ministerio de Ciencia e Innovación (Proyecto No.: PSI2016-80541-P ); UNED (Plan de Promoción de la Investigación) ; y Unión Europea (Proyecto No.: JUST/2013/DPIP/AG/4823-EU MADNESS).
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:RUIdeRA. Repositorio Institucional de la UCLM
instname:Universidad de Castilla-La Mancha
instname_str Universidad de Castilla-La Mancha
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
collection RUIdeRA. Repositorio Institucional de la UCLM
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