The short and long term effects of docetaxel chemotherapy on rodent object recognition and spatial reference memory

Aims

Previous animal studies have examined the potential for cytostatic drugs to induce learning and memory deficits in laboratory animals but, to date, there is no pre-clinical evidence that taxanes have the potential to cause cognitive impairment. Therefore our aim was to explore the short- and long-term cognitive effects of different dosing schedules of the taxane docetaxel (DTX) on laboratory rodents.

Main methods

Healthy male hooded Wistar rats were treated with DTX (6 mg/kg, 10 mg/kg) or physiological saline (control), once a week for 3 weeks (Experiment 1) or once only (10 mg/kg; Experiment 2). Cognitive function was assessed using the novel object recognition (NOR) task and spatial water maze (WM) task 1 to 3 weeks after treatment and again 4 months after treatment.

Key findings

Shortly after DTX treatment, rats perform poorly on NOR regardless of treatment regimen. Treatment with a single injection of 10 mg/kg DTX does not appear to induce sustained deficits in object recognition or peripheral neuropathy.

Significance

Overall these findings show that treatment with the taxane DTX in the absence of cancer and other anti-cancer treatments causes cognitive impairment in healthy rodents.