Modulation of Anxiety-like and Depression-like Dysfunction by Maropitant in Methotrexate-Induced Chemobrain in Mice

İngilizce (OpenAlex)

AbstractBackground: Chemotherapy-related cognitive impairment (CICI) is a major clinical problem. Moreover, significantly reduces the quality of life. Methotrexate (MTX), a widely used antineoplastic agent, is often associated with CICI and causes significant inflammatory, oxidative, and neuroendocrine responses. Maropitant (MAR), a neurokinin-1 receptor blocker, inhibits substance P signaling and may have anti-inflammatory and antioxidant effects. It has become a possible option for reducing chemotherapy-related neurotoxicity; however, its protective effects against MTX-induced neurobehavioral changes are still unclear. Methods: An experimental model of MTX-induced chemobrain was created in mice. The animals received a single dose of MTX (40 mg/kg) 24 hours before behavioral testing. MAR (10 mg/kg, SC) was given in two doses before the MTX injection. Anxiety- and depression-like behaviors were measured using the open field test (OFT) and forced swim test (FST). ELISA tests were performed to measure hippocampal levels of tumor necrosis factor-α (TNF-α) and glutathione GSH. Whereas adrenocorticotropic hormone (ACTH), and corticosterone (CORT) levels were determined using plasma samples. The data were analyzed using one-way ANOVA, followed by the appropriate post hoc tests. Results: MTX caused evident physiological stress; increased corticosterone levels were also detected, along with decreased glutathione levels. MAR treatment significantly mitigated these alterations, reducing the MTX-induced increases in TNF-α, ACTH, and corticosterone, while partially restoring GSN levels and reinstating antioxidant capacity.Conclusion: MAR reduces MTX-induced neuroinflammatory, oxidative, and neuroendocrine changes and improves related behavioral issues. This suggests it may have a therapeutic role in chemotherapy-related neurobehavioral impairment.