Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine rewa
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Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine rewa

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Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine rewa

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dc.contributor.author Giménez Gómez, Pablo
dc.contributor.author Ballestín Hinojosa, Raúl
dc.contributor.author Gil de Biedma-Elduayen, Leticia
dc.contributor.author Vidal, Rebeca
dc.contributor.author Ferrer Pérez, Carmen
dc.contributor.author Reguilón, Marina D.
dc.contributor.author O'Shea, Esther
dc.contributor.author Miñarro López, José
dc.contributor.author Colado, Isabel
dc.contributor.author Rodríguez Arias, Marta
dc.date.accessioned 2021-12-14T16:09:53Z
dc.date.available 2021-12-14T16:09:53Z
dc.date.issued 2021
dc.identifier.uri https://hdl.handle.net/10550/81043
dc.description.abstract 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.
dc.language.iso eng
dc.relation.ispartof Neuropharmacology, 2021, vol. 197:108753, num. 197
dc.rights.uri info:eu-repo/semantics/openAccess
dc.source Giménez Gómez, Pablo Ballestín Hinojosa, Raúl Gil de Biedma-Elduayen, Leticia Vidal, Rebeca Ferrer Pérez, Carmen Reguilón, Marina D. O'Shea, Esther Miñarro López, José Colado, Isabel Rodríguez Arias, Marta 2021 Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine rewa Neuropharmacology 197:108753 197
dc.subject Psicobiologia
dc.title Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine rewa
dc.type info:eu-repo/semantics/article
dc.date.updated 2021-12-14T16:09:54Z
dc.identifier.doi https://doi.org/10.1016/j.neuropharm.2021.108753
dc.identifier.idgrec 148145

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