Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress
- Autores
- Avalos, María Paula; Guzmán, Andrea Susana; Garcia Keller, Constanza; Mongi Bragato, Bethania; Esparza, María Alejandra; Rigoni, Daiana; Sánchez, Marianela A.; Calfa, Gastón Diego; Bollati, Flavia Andrea; Cancela, Liliana Marina
- Año de publicación
- 2022
- Idioma
- español castellano
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Artículo
Fil: Avalos, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Guzmán, Andrea Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Garcia Keller, Constanza. Medical University of South Carolina. Department of Neurosciences; Estados Unidos de Norteamérica.
Fil: Mongi Bragato, Bethania. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Esparza, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Rigoni, Daiana Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Rigoni, Daiana. Université Côte d’Azur; Francia.
Fil: Sánchez, Marianela A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Calfa, Gastón Diego. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.
Fil: Calfa, Gastón Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Fil: Bollati, Flavia Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.
Fil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Fil: Cancela, Liliana Marina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Fil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Though the facilitating influence of stress on drug abuse is well documented, the mechanisms underlying this interaction have yet to be fully elucidated. The present study explores the neurobiological mechanisms underpinning the sensitized response to the psychomotor-stimulating effects of cocaine following chronic restraint stress (CRS), emphasizing the differential contribution of both subcompartments of the nucleus accumbens (NA), the core (NAcore) and shell (NAshell), to this phenomenon. AdultmaleWistar rats were restrained for 2 h/ day for 7 days and, 2 weeks after the last stress exposure (day 21), all animals were randomly assigned to behavioral, biochemical or neurochemical tests. Our results demonstrated that the enduring CRS-induced increase in psychostimulant response to cocaine was paralleled by an increase of extracellular dopamine levels in the NAcore, but not the NAshell, greater than that observed in the non-stress group. Furthermore, we found that CRS induced an impairment of glutamate homeostasis in the NAcore, but not the NAshell. Its hallmarks were increased basal extracellular glutamate concentrations driven by a CRS-induced downregulation of GLT-1, blunted glutamate levels in response to cocaine and postsynaptic structural remodeling in pre-stressed animals. In addition, ceftriaxone, a known GLT-1 enhancer, prevented the CRS-induced GLT-1 downregulation, increased basal extracellular glutamate concentrations and changes in structural plasticity in the NAcore as well as behavioral cross-sensitization to cocaine, emphasizing the biological importance of GLT-1 in the comorbidity between chronic stress exposure and drug abuse. A future perspective concerning the paramount relevance of the stress-induced disruption of glutamate homeostasis as a vulnerability factor to the development of stress and substance use disorders during early life or adulthood of descendants is provided
info:eu-repo/semantics/publishedVersion
Fil: Avalos, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Guzmán, Andrea Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Garcia Keller, Constanza. Medical University of South Carolina. Department of Neurosciences; Estados Unidos de Norteamérica.
Fil: Mongi Bragato, Bethania. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Esparza, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Rigoni, Daiana Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Rigoni, Daiana. Université Côte d’Azur; Francia.
Fil: Sánchez, Marianela A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Fil: Calfa, Gastón Diego. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.
Fil: Calfa, Gastón Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Fil: Bollati, Flavia Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.
Fil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Fil: Cancela, Liliana Marina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina
Fil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina. - Materia
-
chronic restraint stress
ceftriaxone
cocaine
dendritic spines
GLT-1
glutamate
nucleus accumbens
sensitization - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- Repositorio
- Institución
- Universidad Nacional de Córdoba
- OAI Identificador
- oai:rdu.unc.edu.ar:11086/548569
Ver los metadatos del registro completo
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Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stressAvalos, María PaulaGuzmán, Andrea SusanaGarcia Keller, ConstanzaMongi Bragato, BethaniaEsparza, María AlejandraRigoni, DaianaSánchez, Marianela A.Calfa, Gastón DiegoBollati, Flavia AndreaCancela, Liliana Marinachronic restraint stressceftriaxonecocainedendritic spinesGLT-1glutamatenucleus accumbenssensitizationArtículoFil: Avalos, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Guzmán, Andrea Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Garcia Keller, Constanza. Medical University of South Carolina. Department of Neurosciences; Estados Unidos de Norteamérica.Fil: Mongi Bragato, Bethania. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Esparza, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Rigoni, Daiana Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Rigoni, Daiana. Université Côte d’Azur; Francia.Fil: Sánchez, Marianela A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Calfa, Gastón Diego. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.Fil: Calfa, Gastón Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.Fil: Bollati, Flavia Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.Fil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.Fil: Cancela, Liliana Marina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; ArgentinaFil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.Though the facilitating influence of stress on drug abuse is well documented, the mechanisms underlying this interaction have yet to be fully elucidated. The present study explores the neurobiological mechanisms underpinning the sensitized response to the psychomotor-stimulating effects of cocaine following chronic restraint stress (CRS), emphasizing the differential contribution of both subcompartments of the nucleus accumbens (NA), the core (NAcore) and shell (NAshell), to this phenomenon. AdultmaleWistar rats were restrained for 2 h/ day for 7 days and, 2 weeks after the last stress exposure (day 21), all animals were randomly assigned to behavioral, biochemical or neurochemical tests. Our results demonstrated that the enduring CRS-induced increase in psychostimulant response to cocaine was paralleled by an increase of extracellular dopamine levels in the NAcore, but not the NAshell, greater than that observed in the non-stress group. Furthermore, we found that CRS induced an impairment of glutamate homeostasis in the NAcore, but not the NAshell. Its hallmarks were increased basal extracellular glutamate concentrations driven by a CRS-induced downregulation of GLT-1, blunted glutamate levels in response to cocaine and postsynaptic structural remodeling in pre-stressed animals. In addition, ceftriaxone, a known GLT-1 enhancer, prevented the CRS-induced GLT-1 downregulation, increased basal extracellular glutamate concentrations and changes in structural plasticity in the NAcore as well as behavioral cross-sensitization to cocaine, emphasizing the biological importance of GLT-1 in the comorbidity between chronic stress exposure and drug abuse. A future perspective concerning the paramount relevance of the stress-induced disruption of glutamate homeostasis as a vulnerability factor to the development of stress and substance use disorders during early life or adulthood of descendants is providedinfo:eu-repo/semantics/publishedVersionFil: Avalos, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Guzmán, Andrea Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Garcia Keller, Constanza. Medical University of South Carolina. Department of Neurosciences; Estados Unidos de Norteamérica.Fil: Mongi Bragato, Bethania. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Esparza, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Rigoni, Daiana Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Rigoni, Daiana. Université Côte d’Azur; Francia.Fil: Sánchez, Marianela A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.Fil: Calfa, Gastón Diego. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.Fil: Calfa, Gastón Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.Fil: Bollati, Flavia Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.Fil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.Fil: Cancela, Liliana Marina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; ArgentinaFil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.2022-08-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf10.3389/fphys.2022.896268http://hdl.handle.net/11086/548569spahttps://rdu.unc.edu.ar/handle/11086/548507info:eu-repo/semantics/openAccessreponame:Repositorio Digital Universitario (UNC)instname:Universidad Nacional de Córdobainstacron:UNC2025-09-29T13:42:02Zoai:rdu.unc.edu.ar:11086/548569Institucionalhttps://rdu.unc.edu.ar/Universidad públicaNo correspondehttp://rdu.unc.edu.ar/oai/snrdoca.unc@gmail.comArgentinaNo correspondeNo correspondeNo correspondeopendoar:25722025-09-29 13:42:02.6Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdobafalse |
dc.title.none.fl_str_mv |
Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress |
title |
Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress |
spellingShingle |
Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress Avalos, María Paula chronic restraint stress ceftriaxone cocaine dendritic spines GLT-1 glutamate nucleus accumbens sensitization |
title_short |
Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress |
title_full |
Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress |
title_fullStr |
Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress |
title_full_unstemmed |
Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress |
title_sort |
Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress |
dc.creator.none.fl_str_mv |
Avalos, María Paula Guzmán, Andrea Susana Garcia Keller, Constanza Mongi Bragato, Bethania Esparza, María Alejandra Rigoni, Daiana Sánchez, Marianela A. Calfa, Gastón Diego Bollati, Flavia Andrea Cancela, Liliana Marina |
author |
Avalos, María Paula |
author_facet |
Avalos, María Paula Guzmán, Andrea Susana Garcia Keller, Constanza Mongi Bragato, Bethania Esparza, María Alejandra Rigoni, Daiana Sánchez, Marianela A. Calfa, Gastón Diego Bollati, Flavia Andrea Cancela, Liliana Marina |
author_role |
author |
author2 |
Guzmán, Andrea Susana Garcia Keller, Constanza Mongi Bragato, Bethania Esparza, María Alejandra Rigoni, Daiana Sánchez, Marianela A. Calfa, Gastón Diego Bollati, Flavia Andrea Cancela, Liliana Marina |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
chronic restraint stress ceftriaxone cocaine dendritic spines GLT-1 glutamate nucleus accumbens sensitization |
topic |
chronic restraint stress ceftriaxone cocaine dendritic spines GLT-1 glutamate nucleus accumbens sensitization |
dc.description.none.fl_txt_mv |
Artículo Fil: Avalos, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Guzmán, Andrea Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Garcia Keller, Constanza. Medical University of South Carolina. Department of Neurosciences; Estados Unidos de Norteamérica. Fil: Mongi Bragato, Bethania. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Esparza, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Rigoni, Daiana Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Rigoni, Daiana. Université Côte d’Azur; Francia. Fil: Sánchez, Marianela A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Calfa, Gastón Diego. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Fil: Calfa, Gastón Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Fil: Bollati, Flavia Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Fil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Fil: Cancela, Liliana Marina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina Fil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Though the facilitating influence of stress on drug abuse is well documented, the mechanisms underlying this interaction have yet to be fully elucidated. The present study explores the neurobiological mechanisms underpinning the sensitized response to the psychomotor-stimulating effects of cocaine following chronic restraint stress (CRS), emphasizing the differential contribution of both subcompartments of the nucleus accumbens (NA), the core (NAcore) and shell (NAshell), to this phenomenon. AdultmaleWistar rats were restrained for 2 h/ day for 7 days and, 2 weeks after the last stress exposure (day 21), all animals were randomly assigned to behavioral, biochemical or neurochemical tests. Our results demonstrated that the enduring CRS-induced increase in psychostimulant response to cocaine was paralleled by an increase of extracellular dopamine levels in the NAcore, but not the NAshell, greater than that observed in the non-stress group. Furthermore, we found that CRS induced an impairment of glutamate homeostasis in the NAcore, but not the NAshell. Its hallmarks were increased basal extracellular glutamate concentrations driven by a CRS-induced downregulation of GLT-1, blunted glutamate levels in response to cocaine and postsynaptic structural remodeling in pre-stressed animals. In addition, ceftriaxone, a known GLT-1 enhancer, prevented the CRS-induced GLT-1 downregulation, increased basal extracellular glutamate concentrations and changes in structural plasticity in the NAcore as well as behavioral cross-sensitization to cocaine, emphasizing the biological importance of GLT-1 in the comorbidity between chronic stress exposure and drug abuse. A future perspective concerning the paramount relevance of the stress-induced disruption of glutamate homeostasis as a vulnerability factor to the development of stress and substance use disorders during early life or adulthood of descendants is provided info:eu-repo/semantics/publishedVersion Fil: Avalos, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Guzmán, Andrea Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Garcia Keller, Constanza. Medical University of South Carolina. Department of Neurosciences; Estados Unidos de Norteamérica. Fil: Mongi Bragato, Bethania. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Esparza, María Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Rigoni, Daiana Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Rigoni, Daiana. Université Côte d’Azur; Francia. Fil: Sánchez, Marianela A. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Fil: Calfa, Gastón Diego. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Fil: Calfa, Gastón Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Fil: Bollati, Flavia Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina. Fil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Fil: Cancela, Liliana Marina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina Fil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina. |
description |
Artículo |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-08-01 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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10.3389/fphys.2022.896268 http://hdl.handle.net/11086/548569 |
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10.3389/fphys.2022.896268 |
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