Cognitive and Behavioral Effects of Levetiracetam in Juvenile Rats

Epilepsy is a common neurologic disorder; its incidence in childhood is 2.5 per 1000 children. Levetiracetam (LEV) is an antiepileptic drug with a broad spectrum of action used in localized and generalized epilepsies in both adults and children. Studies have shown adverse behavioral effects, such as somnolence, agitation, and nonpsychotic mood disorders in short-term studies. The paucity of properly designed long-term studies to determine the impact of LEV treatment in children encouraged us to analyze the long-term effect of LEV in juvenile Wistar rats. The objective was to study the impact of LEV on cognition and behavior in juvenile rats. Six Wistar rats each were randomly allocated to: Group 1: Control-Received 0.9% NaCl at a dose of 10 mL/kg body weight; 2: Received LEV 200 mg/kg dose; 3: Received LEV 400 mg/kg dose. All drugs were administered once daily orally for 21 days, starting from the third postnatal week to the sixth postnatal week. Compared with the control group, both the 200 mg/kg and 400 mg/kg LEV-treated groups subjected to behavioral paradigms did not decrease learning and memory. Histopathological examination revealed a significant decrease in neuronal density in the dentate gyrus, hippocampus, and frontal cortex in both the 200 mg/kg and 400 mg/kg LEV-treated groups compared with the control group. Although LEV remains a valuable antiepileptic agent, this study highlights the importance of cautious dosing and vigilant monitoring, especially in the long-term use of LEV, as histopathological findings revealed a dose-dependent decrease in the neuronal count.