Effect of prenatal levetiracetam exposure on motor and cognitive functions of rat offspring

Abstract

Purpose. We aimed to establish the physical, motor, and cognitive teratogenic effect of levetiracetam exposure throughout pregnancy in rats. Methods. Thirty-two Sprague Dawley pregnant female rats were divided into four groups. Groups 1-3 were treated with different doses of levetiracetam (25, 50, 100 mg/kg/d) from gestational days 1 to 18. Group 4 (control group) was treated with the same volume of saline. The day of occurrence for pinna detachment, incisor eruption, eye opening, ear opening, and fur development were also monitored. Righting reflex, negative geotaxis, and grip response were evaluated as measures of the development of reflexes. The cognitive and motor developments were established with T-maze, holeboard, Y-maze, locomotor activity, and passive avoidance test. Results. Levetiracetam exposure at 25, 50 and 100 mg/kg/d doses did not affect the timing of physical landmark developments. The dose of 100 mg/kg/d resulted in a significant delay in reaction time of the surface righting reflex compared to the control group. Two higher dose groups (50 and 100 mg/kg/d) had delay in the appearance of negative geotaxis reflex compared to the control group. Both groups maternally exposed to 50 and 100 mg/kg/d had a lower percentage of grip strength response comparing to control group on the first day of testing. On the second test day, only pups prenatally exposed to 100 mg/kg/d levetiracetam persistently had a significantly lower percentage of response. We could not find a significant difference between groups in tests for the locomotor activity, memory, and learning (T- and Y-maze, passive avoidance test), and explorative behavior (holeboard tests). Conclusion. We showed that levetiracetam had only a transient impact on reflex maturation and no impact on physical and cognitive function in offspring of rats exposed to the drug during pregnancy. Levetiracetam may become a promising candidate for the treatment of epileptic women in pregnancy. (c) 2009 Elsevier B.V. All rights reserved.