Sexually Dimorphic Effect of Zonisamide on Behavioral ‎Locomotor Activity in a Rat Model of Parkinson's disease

Ardeshir Moayeri , Zynab Khalili , Marzieh Darvishi

Abstract

Introduction: Zonisamide (ZA) is a new drug that has been shown to be effective ‎against motor damage in Parkinson's disease. However, the behavioral effect of ZA ‎has not been described in male and female of rats. The aim of this study was to ‎evaluate sexually dimorphic effects of ZA on behavioral locomotor activity in a rat ‎model of Parkinson's disease. Materials & Method: 48 adult Wistar rats (24 male ‎and 24 female) were randomly divided into eight groups, consisting of four groups ‎of each sex: 1) sham group 2) PD group (Parkinson's model) 3) ZA group ‎‎(vehicle) and 4) PD plus ZA group (Parkinson's model with ZA treatment). ‎Parkinson's disease was administered by an injection of 6-hydroxydopamine (6-‎HD) into medial forebrain bundles. The drug was orally administered at a dose of ‎‎50 mg / kg every 24 hours for 7 days after surgery. The behavioral effects of ‎apomorphine-induced rotation and spontaneous motor tests (elevated body swing, ‎cylinder, and footfault test) were investigated in rats of both sexes. Results: ZA ‎decreased contralateral rotations in male and female rats compared to the negative ‎control group (p < 0.05) that is correlated with cell loss. ZA improves spontaneous ‎motor tests in both sexes, and this finding is statistically significant. In the PD plus ‎ZA group, the male and female comparisons demonstrated that step through ‎latency in female was higher than that of the male (p  <0 .001). Conclusion: These ‎findings suggest that ZA has positive effects not only on motor and memory ‎function but also on histological symptoms such as cell death in rat PD models‎.