Effect of a TNF-Alpha Inhibitor on Anxiety and Depression-Like Behaviors in a Mouse Chemobrain Model

Abstract

Although chemotherapy increases the survival rate of cancer patients, it causes significant side effects such as deterioration in cognitive functions that generate a decline in their living standards. In our study, the effect of adalimumab on anxiety- and depression-like behaviors in mice with cognitive impairment with methotrexate was investigated. In our study, methotrexate (40 mg kg-1) was administered intraperitoneally as a single dose to create a chemobrain model in mice. Adalimumab (10 mg kg-1), a TNF-alpha inhibitor, was administered twice, 1 hour and 5 days before methotrexate administration. Anxiety-like behaviors were measured with elevated plus maze test and open field test, depression-like behaviors were measured with tail suspension test, and hippocampal tissue was examined histopathologically. Methotrexate decreased the time spent in the central zone in the open-field arena, the time spent in the open arms in the elevated plus maze test, and increased the duration of immobility in the tail suspension test in rats. Methotrexate caused a decrease in the number of neuronal cells in the CA3 region of the hippocampus, as well as neurodegenerative and atrophic changes. Adalimumab ameliorated methotrexate-related anxiety- and depression-like behaviors, and caused improvement in histopathological changes. In this study, it was shown that methotrexate-related anxiety and depression-like behavioral disorders were prevented by adalimumab treatment, but further studies are recommended to investigate the mechanisms mediating the therapeutic effect of adalimumab.