Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations

Behavioral sensitization is a progressive and enduring enhancement of the motor stimulant effects elicited by repeated administration of drugs of abuse. It can be divided into two distinct temporal and anatomical domains, termed initiation and expression, which are characterized by specific molecula...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Cuesta, Santiago, Severin, María Julia, Batuecas, Jorgelina, Rosso, Silvana Beatriz, Pacchioni, Alejandra María
Formato:	article artículo publishedVersion
Lenguaje:	Inglés
Publicado:	Wiley 2018
Materias:	Cocaine Wnt Canonical Pathway Prefrontal Cortex Sensitization Cocaine Neuroadaptations
Acceso en línea:	http://hdl.handle.net/2133/10560 http://hdl.handle.net/2133/10560
Aporte de:	Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario

id	I15-R121-2133-10560
record_format	dspace
institution	Universidad Nacional de Rosario
institution_str	I-15
repository_str	R-121
collection	Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language	Inglés
orig_language_str_mv	eng
topic	Cocaine Wnt Canonical Pathway Prefrontal Cortex Sensitization Cocaine Neuroadaptations
spellingShingle	Cocaine Wnt Canonical Pathway Prefrontal Cortex Sensitization Cocaine Neuroadaptations Cuesta, Santiago Severin, María Julia Batuecas, Jorgelina Rosso, Silvana Beatriz Pacchioni, Alejandra María Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations
topic_facet	Cocaine Wnt Canonical Pathway Prefrontal Cortex Sensitization Cocaine Neuroadaptations
description	Behavioral sensitization is a progressive and enduring enhancement of the motor stimulant effects elicited by repeated administration of drugs of abuse. It can be divided into two distinct temporal and anatomical domains, termed initiation and expression, which are characterized by specific molecular and neurochemical changes. This study examines the role of the Wnt canonical pathway mediating the induction of cocaine sensitization. We found that β-catenin levels in the prefrontal cortex (PFC), amygdala (Amyg) and dorsal striatum (CPu) are decreased in animals that show sensitization. Accordingly, GSK3β activity levels are increased in the same areas. Moreover, β-catenin levels in nuclear fraction, mRNA expression of Axin2 and Wnt7b are decreased in the PFC of sensitized animals. Then, in order to demonstrate that changes in the PFC are crucial for initiation of sensitization, we either rescue β-catenin levels with a systemic treatment of a GSK3β inhibitor (Lithium Chloride) or inhibit Wnt/β-catenin pathway with an intracerebral infusion of Sulindac before each cocaine injection. As expected, rescuing β-catenin levels in the PFC as well as CPu and Amyg blocks cocaine-induced sensitization, while decreasing β-catenin levels exclusively in the PFC exacerbates it. Therefore, our results demonstrate a new role for the Wnt/β-catenin pathway as a required neuroadaptation in inducing behavioral sensitization.
format	article artículo publishedVersion
author	Cuesta, Santiago Severin, María Julia Batuecas, Jorgelina Rosso, Silvana Beatriz Pacchioni, Alejandra María
author_facet	Cuesta, Santiago Severin, María Julia Batuecas, Jorgelina Rosso, Silvana Beatriz Pacchioni, Alejandra María
author_sort	Cuesta, Santiago
title	Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations
title_short	Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations
title_full	Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations
title_fullStr	Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations
title_full_unstemmed	Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations
title_sort	wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations
publisher	Wiley
publishDate	2018
url	http://hdl.handle.net/2133/10560 http://hdl.handle.net/2133/10560
work_keys_str_mv	AT cuestasantiago wntbetacateninpathwayintheprefrontalcortexisrequiredforcocaineinducedneuroadaptations AT severinmariajulia wntbetacateninpathwayintheprefrontalcortexisrequiredforcocaineinducedneuroadaptations AT batuecasjorgelina wntbetacateninpathwayintheprefrontalcortexisrequiredforcocaineinducedneuroadaptations AT rossosilvanabeatriz wntbetacateninpathwayintheprefrontalcortexisrequiredforcocaineinducedneuroadaptations AT pacchionialejandramaria wntbetacateninpathwayintheprefrontalcortexisrequiredforcocaineinducedneuroadaptations
bdutipo_str	Repositorios
_version_	1764820408456970240

Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations

Ejemplares similares