Chemotherapy drug thioTEPA exacerbates stress-induced anhedonia and corticosteroid responses but not impairment of hippocampal cell proliferation in adult mice.

摘要

Cancer patients often suffer long-lasting affective and cognitive impairments as a result of chemotherapy treatment. Previous work in our lab has shown deficits in learning and memory and hippocampal cell proliferation in mice lasting up to 20 weeks following acute administration of thioTEPA. In this study, the effects of thioTEPA in conjunction with effects of chronic stress on depression-related behavior were examined in C57BL/6J mice, 12 weeks following thioTEPA administration. Chemotherapy-treated mice showed a diminished sucralose preference compared to controls that was further exacerbated after 2 weeks of daily restraint stress. This intensifying effect was not observed in the Porsolt forced swim test. Moreover, stress-induced corticosteroid responses were exaggerated in thioTEPA-treated mice. Cell proliferation in the dentate gyrus of the hippocampus was also impaired similarly by prior thioTEPA treatment and by daily restraint stress, with no additive effect. Results suggest that some depression-related impairments may be exacerbated by chemotherapy treatment through altered corticosteroid regulation.