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Título: | Dopamine D3 Receptor Modulates Akt/mTOR and ERK1/2 Pathways Differently during the Reinstatement of Cocaine-Seeking Behavior Induced by Psychological versus Physiological Stress |
Fecha de publicación: | 7-jul-2023 |
Cita bibliográfica: | Int. J. Mol. Sci. 2023, 24, 11214. |
ISSN: | 1422-0067 |
Palabras clave: | cocaine-induced conditioned place preference dopaminergic receptors drug-seeking behavior restraint tail pinch MEK1/2 |
Resumen: | Stress triggers relapses in cocaine use that engage the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and dentate gyrus (DG). Preclinical research suggests that D3 receptor (D3R) antagonists may be a promising means to attenuate cocaine reward and relapse. As D3R regulates the activity of the Akt/mTOR and MEK/ERK1/2 pathways, we assessed the effects of SB-277011-A, a D3R antagonist, on the activity of these kinases during the reinstatement of cocaine-induced conditioned place preference (CPP) induced by psychological (restraint) and physiological (tail pinch) stress. Both stimuli reactivated an extinguished cocaine-CPP, but only restrained animals decreased their locomotor activity during reinstatement. Cocaine-seeking behavior reactivation was correlated with decreased p-Akt, p-mTOR, and p-ERK1/2 activation in both nuclei of restrained animals. While a D3R blockade prevented stress-induced CPP reinstatement and plasma corticosterone enhancement, SB-277011-A distinctly modulated Akt, mTOR, and ERK1/2 activation depending on the stressor and the dose used. Our data support the involvement of corticosterone in the SB-277011-A effects in restrained animals. Additionally, the ratios p-mTOR/mTOR and/or p- ERK1/2 /ERK1/2 in the BLA during stress-induced relapse seem to be related to the locomotor activity of animals receiving 48 mg/kg of the antagonist. Hence, our study indicates the D3R antagonist’s efficacy to prevent stress-induced relapses in drug use through distinct modulation of Akt/mTOR and MEK/ERK1/2 pathways in memory-processing nuclei. |
Autor/es principal/es: | Franco García, Aurelio Guerrero Bautista, Rocío Hidalgo Céspedes, Juana María Gómez Murcia, Victoria Milanés Maquilón, M. Victoria Núñez Parra, María Cristina |
Facultad/Departamentos/Servicios: | Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Farmacología |
URI: | http://hdl.handle.net/10201/132784 |
DOI: | 10.3390/ijms241311214 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 22 |
Derechos: | info:eu-repo/semantics/openAccess |
Descripción: | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). This document is the published version of a published work that appeared in final form in International Journal of Molecular Sciences. To access the final edited and published work see https:// doi.org/10.3390/ijms241311214 |
Aparece en las colecciones: | Artículos: Farmacología |
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Int J Mol Sci’23.pdf | Int. J. Mol. Sci. 2023, 24, 11214. https://doi.org/10.3390/ijms241311214. | 5,11 MB | Adobe PDF | Visualizar/Abrir |
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