Atomoxetine improves hippocampal cell proliferation but not memory in Doxorubicin-treated adult male rats

Abstract

Atomoxetine (ATX) is a noradrenaline reuptake inhibitor used to treat Attention deficit hyperactive disorder (ADHD), or improve cognition in normal subjects. Cancer patients treated with systemic adjuvant chemotherapy have described experiencing deterioration in cognition. Doxorubicin (DOX, Adriamycin) is one of the anthracycline families used in chemotherapy, which has a deteriorating effect on both cognition and proliferation. The cognitive effects of ATX require inputs from the hippocampus. The aim of this study was to examine spatial memory and proliferation in the subgranular zone (SGZ) of the DG in adult Lister Hooded rats treated either alone or with a combination of Atomoxetine (30 mg kg−1 day−1, six i.p. doses, one injection every other day) and Doxorubicin (DOX) (2 mg kg−1 day−1, six i.p. doses, one injection every other day). Spatial memory was tested using the Novel location recognition (NLR) test, and proliferation of hippocampal cells was quantified using immunohistochemistry for the proliferative marker Ki67. Results showed that ATX treatment has improved the NLR task and increased cell proliferation in the SGZ of the DG, compared with saline-treated controls. Animals treated with DOX only showed deficits in NLR task, and co-administration of ATX along with DOX did not improve their performance. DOX chemotherapy caused a significant reduction in the number of proliferating cells in the SGZ of the DG compared with saline-treated controls. This reduction was reversed by co-administration of ATX. The above findings suggest that DOX can negatively affect both cell proliferation and memory and ATX co-administration improves proliferation, but not memory in the adult male rat hippocampus.