Differential Effects of Valproic Acid on Immobility Responses and Locomotor Activity in Female and Male Rats

Abstract

Valproic acid (VPA) is used in the treatment of epilepsy and behavioral disorders. However, the exposure to VPA during pregnancy increases the risk of having offspring with autism spectrum disorder (ASD). Reports indicate that men are more likely to suffer ASD than women who were exposed to VPA prenatally. Few studies have related the sex differences and behavioral changes in the ASD rat model. Our aim was to determinate whether male and female Wistar rats whose mothers were exposed to either VPA (600 mg/kg; animal model for ASD) or saline (0.9%) i.p. at 12.5 day of gestation, have different effects on immobility induce by clamping (IC), dorsal immobility (DI), catalepsy, locomotor activity, stereotypes, and analgesia (tail flick). For this purpose, we made four groups (n = 8). Group: A) saline male rats, B) saline female rats, C) VPA male rats and D) VPA female rats. At 35 (prepubertal age), 56 (postpubertal age) and 180 days, we tested the behaviors previously mentioned. Finding that VPA has the same effect on IC, catalepsy, and analgesia in male and female rats, the time of these tests was increased. However, VPA only has an effect on DI in males but not in female rats. On the contrary, there is hyperactivity and an increase of stereotypes in female but not in male rats. Thereby, VPA has an effect on the three immobility responses tested (IC, DI and catalepsy), locomotor activity and analgesia but in a differential way on DI, stereotypes and locomotor activity between male and female rats.