Rescuing Behavioral Impairment after Doxorubicin Chemotherapy in Rats

Abstract

Chemotherapy regimens have been extensively used for the treatment of various types of cancers. Despite the effectiveness of this treatment, clinical use of chemotherapeutic agents often produces negative side effects like deficits in cognition and memory, delayed processing speed, and executive function. This condition is widely recognized as chemotherapy‐induced cognitive impairment or “Chemo brain.” Our study aimed to identify the neurobiological mechanisms possibly responsible for this cognitive impairment. We examined the effects of chronic treatment with the chemotherapeutic drug Doxorubicin on cognitive impairment. Doxorubicin is a reactive oxygen species‐producing antineoplastic Anthracycline agent that adversely affects hippocampal neurogenesis, causes neuro‐inflammation, and induces apoptosis. Baseline activity data were collected and then twelve young female Long Evans hooded rats were randomly assigned to receive either Doxorubicin (6mg/kg) or 0.9% saline given intraperitoneally, once weekly for four weeks. After treatment, rats were assessed on the string‐pulling task, the bar walk test, and open field test. Two individuals blind to the treatment calculated the average time duration, number of attempts to pull the string, number of misses, total number of mouth contacts before and after treatment for the string‐pulling task, number of deep slips, slight slips, and the total number of slips for the bar walk test. Similarly, the number of entries to the center, number of entries to the corners, time spent at the center vs corner, and latency to first enter and exit the center was calculated for the open field test and compared between two groups. No significant differences were detected between Dox‐treated and Control rats on any measure, which suggests that the Dox‐treatment produced little or no significant peripheral neuropathy that disrupted performance on the motor tasks we used and did not induce significant anxiety in our rats. Immuno‐histochemical analyses of brain tissues is ongoing to examine markers of neurogenesis and neuro‐inflammation.