Gender difference in motor impairments induced by chronic administration of vinblastine.

Abstract

Neurotoxicity of anticancer drugs complicates treatment of cancer patients. Vinblastine (VBL) is reported to induce motor and cognitive impairments in patients receiving chronic low-dose regimen. The effects of VBL treatment on motor, learning and memory functions of male and female Wistar rats were studied by behavioral related tests. Animals were given chronic intraperitoneal injections of VBL (0.2 mg/kg/week for 5 weeks) from postnatal day 23 to 52. Motor function was evaluated using grasping test and balancing was evaluated by the rotarod. Spatial learning and memory and anxiety-like behavior were determined using Morris water maze (MWM) task and open field test, respectively. Administration of VBL caused severe damage to motor and balance function of male rats in comparison to female rats treated with VBL and rats treated with saline. Memory and locomotion were affected in both male and female rats compared with saline treated rats, while a sex difference was also observed in these parameters; male rats showed more impairment compared with female ones. Both male and female rats showed cognitive impairments in MWM task and no sex differences were observed in these functions. Results revealed that VBL is a potent neurotoxic agent and despite the profound effect of VBL on motor and cognitive functions, it seems that male rats are more susceptible to motor deficits induced by VBL.