Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine reward
Giménez-Gómez, Pablo ; Ballestín, Raúl ; Gil de Biedma-Elduayen, Leticia ; Vidal, Rebeca ; Ferrer-Pérez, Carmen (Universidad de Zaragoza) ; Reguilón, Marina D. ; O'Shea, Esther ; Miñarro, José ; Colado, María Isabel ; Rodríguez-Arias, Marta
Resumen: The kynurenine (KYN) pathway of tryptophan (TRP) degradation is activated by stress and inflammatory factors. It is now well established that social stress induces the activation of the immune system, with central inflammation and KYN metabolism being two of the main factors linking stress with depression.
The aim of the present study was to evaluate the long-lasting changes in the KYN pathway induced by social defeat (SD) associated with the resilience or susceptibility to an increase in the conditioned rewarding effects of cocaine. Mice were exposed to repeated SD and 3 weeks later, a conditioned place preference (CPP) induced by a subthreshold dose of cocaine (1.5 mg/kg) was developed. KYN levels in plasma, cerebellum, hippocampus, striatum and limbic forebrain were studied at the end of the CPP procedure. Changes in the KYN pathway after exposure to pharmacological (oxytocin and indomethacin) and environmental interventions (environmental enrichment) were also evaluated.
Our results showed that defeated susceptible (SD-S) mice had higher conditioning scores than resilient mice (SD-R). In addition, although KYN concentration was elevated in all defeated mice, SD-R mice showed smaller increases in KYN concentration in the cerebellum than SD-S mice. Oxytocin or Indomethacin treatment before SD normalized cocaine-induced CPP, although the increase in the KYN pathway was maintained. However, environmental enrichment before SD normalized cocaine-induced CPP and prevented the increase in the KYN pathway.
The present study highlights the role of the KYN pathway and anti-inflammatory drugs acting on TRP metabolism as pharmacological targets to potentiate resilience to social stress effects.
Idioma: Inglés
DOI: 10.1016/j.neuropharm.2021.108753
Año: 2021
Publicado en: NEUROPHARMACOLOGY 197 (2021), 108753 [16 pp.]
ISSN: 0028-3908
Factor impacto JCR: 5.273 (2021)
Categ. JCR: PHARMACOLOGY & PHARMACY rank: 66 / 279 = 0.237 (2021) - Q1 - T1
Categ. JCR: NEUROSCIENCES rank: 82 / 275 = 0.298 (2021) - Q2 - T1
Factor impacto CITESCORE: 9.6 - Neuroscience (Q1) - Pharmacology, Toxicology and Pharmaceutics (Q1)
Factor impacto SCIMAGO: 1.323 - Pharmacology (Q1) - Cellular and Molecular Neuroscience (Q1)
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-105847RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PSI2017-83023-R
Tipo y forma: Article (Published version)
Área (Departamento): Área Psicolog.Evolut.Educac (Dpto. Psicología y Sociología)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material.
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The aim of the present study was to evaluate the long-lasting changes in the KYN pathway induced by social defeat (SD) associated with the resilience or susceptibility to an increase in the conditioned rewarding effects of cocaine. Mice were exposed to repeated SD and 3 weeks later, a conditioned place preference (CPP) induced by a subthreshold dose of cocaine (1.5 mg/kg) was developed. KYN levels in plasma, cerebellum, hippocampus, striatum and limbic forebrain were studied at the end of the CPP procedure. Changes in the KYN pathway after exposure to pharmacological (oxytocin and indomethacin) and environmental interventions (environmental enrichment) were also evaluated.
Our results showed that defeated susceptible (SD-S) mice had higher conditioning scores than resilient mice (SD-R). In addition, although KYN concentration was elevated in all defeated mice, SD-R mice showed smaller increases in KYN concentration in the cerebellum than SD-S mice. Oxytocin or Indomethacin treatment before SD normalized cocaine-induced CPP, although the increase in the KYN pathway was maintained. However, environmental enrichment before SD normalized cocaine-induced CPP and prevented the increase in the KYN pathway.
The present study highlights the role of the KYN pathway and anti-inflammatory drugs acting on TRP metabolism as pharmacological targets to potentiate resilience to social stress effects.
Idioma: Inglés
DOI: 10.1016/j.neuropharm.2021.108753
Año: 2021
Publicado en: NEUROPHARMACOLOGY 197 (2021), 108753 [16 pp.]
ISSN: 0028-3908
Factor impacto JCR: 5.273 (2021)
Categ. JCR: PHARMACOLOGY & PHARMACY rank: 66 / 279 = 0.237 (2021) - Q1 - T1
Categ. JCR: NEUROSCIENCES rank: 82 / 275 = 0.298 (2021) - Q2 - T1
Factor impacto CITESCORE: 9.6 - Neuroscience (Q1) - Pharmacology, Toxicology and Pharmaceutics (Q1)
Factor impacto SCIMAGO: 1.323 - Pharmacology (Q1) - Cellular and Molecular Neuroscience (Q1)
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-105847RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PSI2017-83023-R
Tipo y forma: Article (Published version)
Área (Departamento): Área Psicolog.Evolut.Educac (Dpto. Psicología y Sociología)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you may not distribute the modified material. Exportado de SIDERAL (2023-05-18-14:38:39)
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Record created 2022-01-15, last modified 2023-05-19