Amisulpride Ameliorates 5-Fluorouracil-Induced Memory Deficits in Wistar Rats

Abstract

Abstract Mounting evidence reports chemotherapy-induced cognitive impairments in a significant number of cancer survivors which is known as “chemo-brain”. 5-fluorouracil (5-FU) is a widely used chemotherapeutic agent that crosses the blood–brain barrier readily and may have a direct brain neurotoxic effect. Moreover, 5 FU has been reported to affect cognition and hippocampal neurogenesis. In contrast, studies reveal the enhancement of cognition and hippocampal neurogenesis by atypical antipsychotics such as amisulpride. In this study the behavioural effects of chronic amisulpride therapy have been investigated in 5-FU-exposed adult Wistar rats. Behavioural effects were tested using the novel object recognition test (NORT) and the object location test (OLT). 5-FU-exposed rats exhibited significant deficits in object recognition and object location tasks. Moreover, 5-FU chemotherapy induced a significant reduction in hippocampal brain derived neurotrophic factor compared to control group. These deficits were alleviated following chronic amisulpride treatment. These findings suggest that 5-FU therapy can negatively affect both neurogenesis and hippocampal dependent working memory and that these deficits can be reversed by the simultaneous administration of the atypical antipsychotic amisulpride.