Iranian Journal of Medical Sciences

Document Type: Original Article(s)


1 Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran

2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran


Background: Antiepileptic drugs, such as valproate sodium (VS), are teratogenic as their usage by the pregnant mother has been associated with an increased risk of major congenital abnormalities in the fetus. In this study, the effects of voluntary exercise and prenatal exposure to Valproate Sodium (VS) on learning, memory, and anxiety in rats’ offspring are investigated.
Methods: In the present study, 70 female albino Wistar rats (200-240g) were used. The rats were categorized in seven groups: 1&2, pregnant rats with exposure to VS (10 mg/kg/day i.p) with voluntary exercise and sedentary; 3&4, pregnant rats with exposure to VS (20 mg/kg/day i.p) with voluntary exercise and sedentary; 5&6 pregnant rats with exposure to normal saline (0.4 ml/day i.p) with voluntary exercise and sedentary; 7, pregnant rats with exposure to lamotrigine (20 mg/kg/day i.p). Learning and memory were tested in male offspring using shuttle-box; anxiety were tested by elevated plus-maze (each group n=12). Statistical analyses were performed using the one-way ANOVA (the Tukey test) and/or two-way ANOVA on rank by Graph Pad Prism (7.0) software.
Results: The results showed that voluntary exercise in male rats caused improvement of latency and duration time in the dark box compared to sedentary groups (P=0.004). Also, the group which was administrated to 10 mg/kg VS showed better learning capability than the group administrated to 20 mg/kg VS. Voluntary exercise could also improve anxiety (P=0.001).
Conclusion: This study indicated that exercise could increase learning capacity and improve memories in rats’ offspring that their mothers were exposed to VS. Voluntary exercise can improve anxiety too, and the effect is dose-dependent.