TITLE:
Differential Effects of Valproic Acid on Immobility Responses and Locomotor Activity in Female and Male Rats
AUTHORS:
Oscar Morales-Dionisio, Fidel de la Cruz, Margarita Franco-Colín, Oriana Hidalgo-Alegría, Gonzalo Flores, José Luna-Muñoz, Linda Garcés-Ramírez
KEYWORDS:
Autism, Immobility Responses, Animal Model for ASD, Locomotor Activity, Valproic Acid
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.8 No.10,
October
24,
2017
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.