Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress

Registro completo

Título

Impairment of glutamate homeostasis in the nucleus accumbens core underpins cross-sensitization to cocaine following chronic restraint stress

Autor(es)

Avalos, Maria Paula; Bollati, Flavia Andrea; Calfa, Gaston Diego; Sanchez, Marianela Adela; Rigoni, Daiana; Esparza, Maria Alejandra; Mongi Bragato, Bethania del Carmen; Garcia Keller, Constanza; Guzman, Andrea Susana; Cancela, Liliana Marina

Afiliación(es) del/de los autor(es)

Avalos, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Cancela, Liliana Marina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.
Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Bollati, Flavia Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.
Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Rigoni, Daiana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Garcia Keller, Constanza. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Guzmán, Andrea Susana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Calfa, Diego Gastón. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Calfa, Diego Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Sanchez, Marianela Adela. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Sanchez, Marianela Adela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Esparza, Maria Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Esparza, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Farmacología Experimental de Córdoba; Argentina.
Mongi Bragato, Bethania del Carmen. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina.
Mongi Bragato, Bethania del Carmen. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; Argentina.

Resumen

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. Adult male Wistar 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

Año de publicación

2022

Idioma

inglés

Formato (Tipo MIME)

application/zip

Clasificación temática de acuerdo a la FORD

Ciencias médicas y de la salud

Materia

Chronic restraint stress; Ceftriaxone; Cocaine; Dendritic spines; GLT-1; Glutamate; Nucleus accumbens; Sensitization;

Condiciones de uso

Disponible en acceso abierto

Repositorio digital

Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdoba

Registro relacionado

https://rdu.unc.edu.ar/handle/11086/548569