Behavioral standardization and validation of a new model of cancer-induced depression in sarcoma-bearing mice.

Abstract

Cancer has been correlated with psychiatrical disorders, and incidence of depression is about 3-fold higher in oncological patients. However, there is no validated animal models currently describing sarcoma-associated depression. Herein, we evaluated a preclinical way for estimating behavioral depression-like parameters in Sarcoma-180180180-transplanted mice and investigated the therapeutic efficacy of current clinical antidepressants. Firstly, S-180-bearing Swiss were evaluated using behavioral tests between days 10-11 after S-180 transplantation: open field (OFT), elevated plus maze (EPM), light-dark box (LDB), tail suspension (TST), forced swim (FST), and sucrose preference (SPT). Next, studies investigated effects of amitriptyline (AMI, oral), fluoxetine (FLU, oral), or 5-fluorouracil (5-FU, i.p.) at 10 or 20 mg/kg/day (alone or in combination) on behavior and oxidative/nitrosative profile of subacute-treated mice. No significant differences (p> 0.05) were observed about locomotor and exploratory activity (OFT, EPM, LDB). Meanwhile, S-180-bearing mice showed increase of immobility time (TST) and reduced sucrose preference in comparison with healthy animals (p< 0.05), typical features of depressive phenotype without alterations in anxiety-related parameters. These findings were associated with oxidative stress (malondialdehyde increasing) and antioxidant markers (superoxide dismutase decreasing/increasing) in the prefrontal cortex and/or hippocampus (p< 0.05). Such biochemical changes and depressive phenotype were partly attenuated by amitriptyline and fluoxetine 10 or 20 mg/kg/day for 10 days, but co-treatment with 5-FU did not show additional improvements. This physiopathological study represent a promising discovery highlighting the potential of non-clinical protocols to understand mesenchymal tumor-related depression and to develop new pharmacological tools against the multivariate spectrum of cancer-related diseases.