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

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dc.creator Cuesta, Santiago
dc.creator Severin, María Julia
dc.creator Batuecas, Jorgelina
dc.creator Rosso, Silvana B.
dc.creator Pacchioni, Alejandra Maria
dc.date.accessioned 2018-02-20T22:34:10Z
dc.date.available 2018-02-20T22:34:10Z
dc.date.issued 2017-07
dc.identifier.issn 1369-1600 es
dc.identifier.uri http://hdl.handle.net/2133/10560
dc.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. es
dc.description.sponsorship Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT), PICT 227-2008 es
dc.format application/pdf
dc.format.extent 933-945 es
dc.language.iso eng es
dc.publisher Wiley es
dc.rights openAccess es
dc.subject Cocaine es
dc.subject Wnt Canonical Pathway es
dc.subject Prefrontal Cortex es
dc.subject Sensitization es
dc.subject Cocaine Neuroadaptations es
dc.title Wnt/beta-catenin pathway in the prefrontal cortex is required for cocaine-induced neuroadaptations es
dc.type article
dc.type artículo
dc.type publishedVersion
dc.rights.holder Wiley es
dc.rights.holder Society for the Study of Addiction es
dc.rights.holder Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas es
dc.rights.holder Cuesta, Santiago es
dc.rights.holder Severin, Maria Julia es
dc.rights.holder Batuecas, Jorgelina es
dc.rights.holder Rosso, Silvana B. es
dc.rights.holder Pacchioni, Alejandra María es
dc.relation.publisherversion http://onlinelibrary.wiley.com/doi/10.1111/adb.12377/abstract es
dc.relation.publisherversion http://dx.doi.org/doi:10.1111/adb.12377 es
dc.rights.text Attribution-NonCommercial 4.0 International es
dc.citation.title Addiction Biology es
dc.citation.volume 22(4) es
dc.description.fil Fil: Cuesta, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina. es
dc.description.fil Fil: Cuesta, Santiago. Douglas Mental Health University Institute; Canada. es
dc.description.fil Fil: Cuesta, Santiago. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Ciencias de los Alimentos y del Medioambiente. Área Toxicología; Argentina. es
dc.description.fil Fil: Severin, María Julia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Ciencias de los Alimentos y del Medioambiente. Área Toxicología; Argentina. es
dc.description.fil Fil: Batuecas, Jorgelina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Ciencias de los Alimentos y del Medioambiente. Área Toxicología; Argentina. es
dc.description.fil Fil: Rosso, Silvana B. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina. es
dc.description.fil Fil: Rosso, Silvana B. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Ciencias de los Alimentos y del Medioambiente. Área Toxicología; Argentina. es
dc.description.fil Fil: Pacchioni, Alejandra María. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina. es
dc.description.fil Fil: Pacchioni, Alejandra María. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Ciencias de los Alimentos y del Medioambiente. Área Toxicología; Argentina. es
dc.type.collection articulo
dc.type.version publishedVersion es


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