European journal of pharmacology · 2025
The interplay between Kynurenine and Nociceptin/Orphanin FQ pathways can be related to depressive-like phenotype.
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Câmara Alice Barros, Brandão Igor Augusto
Аннотация
AIMS: This study aims to evaluate whether systemic administration of a nociceptin/orphanin FQ peptide (NOP) receptor agonist and exposure to the social defeat protocol are associated with upregulation of Kynurenine pathway. Additionally, we aim to investigate the potential association between NOP receptor-induced Kynurenine upregulation and markers of oxidative stress, neuroinflammation, and depressive-like behaviors.
METHODS: Behavioral tests were applied to evaluate depressive behavior in male Swiss mice submitted to social defeat protocol and treated with Ro 65-6570 (1.5 or 2 mg/kg; IP). Biochemical analyses were performed in the animals' brains and blood using spectrophotometry and ELISA. The software SPSS v.29 and R programming language were used to analyze the data.
RESULTS: High concentrations of Kynurenine were detected in the hippocampus, prefrontal cortex, and serum of animals treated with Ro 65-6570 and submitted to the social defeat protocol. In the prefrontal cortex, high doses of the agonist combined with the defeat protocol were associated with the Kynurenine upregulation. In the hippocampus, administration of the NOP agonist alone was associated with Kynurenine upregulation. Kynurenine levels were negatively correlated with the gain of weight, distance traveled, and interaction time of animals, as well as with IL-10 concentrations in the hippocampus, while Kynurenine levels were positively correlated with the immobility time of animals, IL-6 and carbonylated protein levels, as well as malondialdehyde in serum.
CONCLUSION: Neuroinflammatory and oxidative effects related to the NOP receptor activation may contribute to the Kynurenine upregulation and this indirect interaction between Nociceptin and Kynurenine pathways can be related to sub-chronic depressive phenotype.
METHODS: Behavioral tests were applied to evaluate depressive behavior in male Swiss mice submitted to social defeat protocol and treated with Ro 65-6570 (1.5 or 2 mg/kg; IP). Biochemical analyses were performed in the animals' brains and blood using spectrophotometry and ELISA. The software SPSS v.29 and R programming language were used to analyze the data.
RESULTS: High concentrations of Kynurenine were detected in the hippocampus, prefrontal cortex, and serum of animals treated with Ro 65-6570 and submitted to the social defeat protocol. In the prefrontal cortex, high doses of the agonist combined with the defeat protocol were associated with the Kynurenine upregulation. In the hippocampus, administration of the NOP agonist alone was associated with Kynurenine upregulation. Kynurenine levels were negatively correlated with the gain of weight, distance traveled, and interaction time of animals, as well as with IL-10 concentrations in the hippocampus, while Kynurenine levels were positively correlated with the immobility time of animals, IL-6 and carbonylated protein levels, as well as malondialdehyde in serum.
CONCLUSION: Neuroinflammatory and oxidative effects related to the NOP receptor activation may contribute to the Kynurenine upregulation and this indirect interaction between Nociceptin and Kynurenine pathways can be related to sub-chronic depressive phenotype.