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
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:dnet:ruidera_____::f089a8b3438338aee356c2205ab89623
Acesso em linha: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
Palavra-chave: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 rats Marcos, Alberto Ballesteros Yáñez, Inmaculada Castillo Sarmiento, Carlos Alberto Pardo, Felipe Roura Martínez, David Muñoz Rodríguez, José Ramón Higueras Matas, Alejandro Ambrosio, Emilio Co-abuse Cocaine Ethanol GABAergic Glutamatergic and endocannabinoid systems Mesocorticolimbic system Rat 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. Elsevier 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
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
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
topic Co-abuse
Cocaine
Ethanol
GABAergic
Glutamatergic and endocannabinoid systems
Mesocorticolimbic system
Rat
topic_facet 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
format article
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
eu_rights_str_mv openAccess
publisher Elsevier
institution Universidad de Castilla-La Mancha
collection RUIdeRA. Repositorio Institucional de la UCLM
reponame_str RUIdeRA. Repositorio Institucional de la UCLM
instname_str Universidad de Castilla-La Mancha
_version_ 1878439868718120960
publishDateSort 2022
author_browse Ambrosio, Emilio
Ballesteros Yáñez, Inmaculada
Castillo Sarmiento, Carlos Alberto
Higueras Matas, Alejandro
Marcos, Alberto
Muñoz Rodríguez, José Ramón
Pardo, Felipe
Roura Martínez, David
publisherStr Elsevier
score 6.9303427

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