Adverse Aftereffects of Methotrexate as Chemotherapy on Cognitive Deficits in Rat Models

Patients with acute lymphoblastic leukemia have a high five-year survival rate thanks to methotrexate (MTX). However, cognitive side effects are reported, characterized as chemo brain. The study investigated if impulsiveness is part of the aberrant cognitive functions after being exposed to MTX in the early stage of physical development. Adolescent rats were injected with either phosphate-buffered saline (PBS) or MTX. The novel object recognition (NOR) task was conducted a month after the injections to measure the memory deficits. The discounting task was performed after the rats completed training on a fixed-ratio one schedule for both levers. The NOR test showed both the PBS and MTX rats recognized the novel object; however, the PBS group spent more time inspecting the novel object than the MTX group. Initial results from two rats (one from each group) for the discounting task showed that the PBS-treated rat preferred the immediate reward at the beginning and had increased omissions during the later trials. The MTX rat showed a consistent preference for the immediate lever across the entire procedure. These composite findings suggested cognitive deficits are not apparent within one month of MTX treatment, yet the impulsiveness is more apparent after MTX exposure