Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration

Autores
Garcia Keller, Constanza; Kupchik, Y.M.; Gipson, C.D.; Brown, R. M.; Spencer, S.; Bollati, Flavia Andrea; Esparza, Maria Alejandra; Roberts Wolfe, D.J.; Heinsbroek, J. A.; Bobadilla, A. C.; Cancela, Liliana Marina; Kalivas, P. W.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders.
Fil: Garcia Keller, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Medical University of South Carolina; Estados Unidos
Fil: Kupchik, Y.M.. The Hebrew University of Jerusalem; Israel
Fil: Gipson, C.D.. Medical University of South Carolina; Estados Unidos
Fil: Brown, R. M.. University of Melbourne; Australia
Fil: Spencer, S.. Medical University of South Carolina; Estados Unidos
Fil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
Fil: Esparza, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
Fil: Roberts Wolfe, D.J.. Medical University of South Carolina; Estados Unidos
Fil: Heinsbroek, J. A.. Medical University of South Carolina; Estados Unidos
Fil: Bobadilla, A. C.. Medical University of South Carolina; Estados Unidos
Fil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
Fil: Kalivas, P. W.. Medical University of South Carolina; Estados Unidos
Materia
Self Administration
Acute Stress
Cocaine
Glutamate
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/50402
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administrationGarcia Keller, ConstanzaKupchik, Y.M.Gipson, C.D.Brown, R. M.Spencer, S.Bollati, Flavia AndreaEsparza, Maria AlejandraRoberts Wolfe, D.J.Heinsbroek, J. A.Bobadilla, A. C.Cancela, Liliana MarinaKalivas, P. W.Self AdministrationAcute StressCocaineGlutamatehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders.Fil: Garcia Keller, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Medical University of South Carolina; Estados UnidosFil: Kupchik, Y.M.. The Hebrew University of Jerusalem; IsraelFil: Gipson, C.D.. Medical University of South Carolina; Estados UnidosFil: Brown, R. M.. University of Melbourne; AustraliaFil: Spencer, S.. Medical University of South Carolina; Estados UnidosFil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Esparza, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Roberts Wolfe, D.J.. Medical University of South Carolina; Estados UnidosFil: Heinsbroek, J. A.. Medical University of South Carolina; Estados UnidosFil: Bobadilla, A. C.. Medical University of South Carolina; Estados UnidosFil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Kalivas, P. W.. Medical University of South Carolina; Estados UnidosNature Publishing Group2016-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/50402Garcia Keller, Constanza; Kupchik, Y.M.; Gipson, C.D.; Brown, R. M.; Spencer, S.; et al.; Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration; Nature Publishing Group; Molecular Psychiatry; 21; 8; 8-2016; 1063-10691359-41841476-5578CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/mp.2015.151info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/mp2015151info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823171/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:16:40Zoai:ri.conicet.gov.ar:11336/50402instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:16:41.117CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration
title Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration
spellingShingle Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration
Garcia Keller, Constanza
Self Administration
Acute Stress
Cocaine
Glutamate
title_short Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration
title_full Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration
title_fullStr Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration
title_full_unstemmed Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration
title_sort Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration
dc.creator.none.fl_str_mv Garcia Keller, Constanza
Kupchik, Y.M.
Gipson, C.D.
Brown, R. M.
Spencer, S.
Bollati, Flavia Andrea
Esparza, Maria Alejandra
Roberts Wolfe, D.J.
Heinsbroek, J. A.
Bobadilla, A. C.
Cancela, Liliana Marina
Kalivas, P. W.
author Garcia Keller, Constanza
author_facet Garcia Keller, Constanza
Kupchik, Y.M.
Gipson, C.D.
Brown, R. M.
Spencer, S.
Bollati, Flavia Andrea
Esparza, Maria Alejandra
Roberts Wolfe, D.J.
Heinsbroek, J. A.
Bobadilla, A. C.
Cancela, Liliana Marina
Kalivas, P. W.
author_role author
author2 Kupchik, Y.M.
Gipson, C.D.
Brown, R. M.
Spencer, S.
Bollati, Flavia Andrea
Esparza, Maria Alejandra
Roberts Wolfe, D.J.
Heinsbroek, J. A.
Bobadilla, A. C.
Cancela, Liliana Marina
Kalivas, P. W.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Self Administration
Acute Stress
Cocaine
Glutamate
topic Self Administration
Acute Stress
Cocaine
Glutamate
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders.
Fil: Garcia Keller, Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina. Medical University of South Carolina; Estados Unidos
Fil: Kupchik, Y.M.. The Hebrew University of Jerusalem; Israel
Fil: Gipson, C.D.. Medical University of South Carolina; Estados Unidos
Fil: Brown, R. M.. University of Melbourne; Australia
Fil: Spencer, S.. Medical University of South Carolina; Estados Unidos
Fil: Bollati, Flavia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
Fil: Esparza, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
Fil: Roberts Wolfe, D.J.. Medical University of South Carolina; Estados Unidos
Fil: Heinsbroek, J. A.. Medical University of South Carolina; Estados Unidos
Fil: Bobadilla, A. C.. Medical University of South Carolina; Estados Unidos
Fil: Cancela, Liliana Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentina
Fil: Kalivas, P. W.. Medical University of South Carolina; Estados Unidos
description There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology. We also determined whether acute stress potentiated the acquisition of cocaine self-administration. Acute stress produced an enduring reduction in glutamate transport and potentiated excitatory synapses on medium spiny neurons. Acute stress also augmented the acquisition of cocaine self-administration. Importantly, by restoring glutamate transport in the accumbens core with ceftriaxone the capacity of acute stress to augment the acquisition of cocaine self-administration was abolished. Similarly, ceftriaxone treatment prevented stress-induced potentiation of cocaine-induced locomotor activity. However, ceftriaxone did not reverse stress-induced synaptic potentiation, indicating that this effect of stress exposure did not underpin the increased acquisition of cocaine self-administration. Reversing acute stress-induced vulnerability to self-administer cocaine by normalizing glutamate transport poses a novel treatment possibility for reducing comorbid SUDs in stress disorders.
publishDate 2016
dc.date.none.fl_str_mv 2016-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/50402
Garcia Keller, Constanza; Kupchik, Y.M.; Gipson, C.D.; Brown, R. M.; Spencer, S.; et al.; Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration; Nature Publishing Group; Molecular Psychiatry; 21; 8; 8-2016; 1063-1069
1359-4184
1476-5578
CONICET Digital
CONICET
url http://hdl.handle.net/11336/50402
identifier_str_mv Garcia Keller, Constanza; Kupchik, Y.M.; Gipson, C.D.; Brown, R. M.; Spencer, S.; et al.; Glutamatergic mechanisms of comorbidity between acute stress and cocaine self-administration; Nature Publishing Group; Molecular Psychiatry; 21; 8; 8-2016; 1063-1069
1359-4184
1476-5578
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823171/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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