RT Journal Article
T1 Decreased kynurenine pathway potentiate resilience to social defeat effect on cocaine reward
A1 Ballestín, Raúl
A1 Ferrer Pérez, Carmen
A1 Reguilón, Marina D
A1 Miñarro López, José
A1 Rodríguez Arias, Marta
A1 Giménez Gómez, Pablo
A1 Gil De Biedma Elduayen, Leticia
A1 Vidal Casado, Rebeca
A1 O'Shea Gaya, María Esther
A1 Colado Megías, María Isabel
AB 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.
PB Elsevier
YR 2021
FD 2021-10-01
LK https://hdl.handle.net/20.500.14352/104601
UL https://hdl.handle.net/20.500.14352/104601
LA eng
NO Ministerio de Economía y Competitividad, Dirección General de Investigación
NO Ministerio de Ciencia e Innovación
NO Ministerio de Sanidad, Consumo y Bienestar Social
NO Universidad Complutense de Madrid
NO Instituto de Salud Carlos III, Red de Trastornos Adictivos
NO Unión Europea
DS Docta Complutense
RD 4 abr 2025