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Cognitive and Behavioral Effects of Levetiracetam in Juvenile Rats
Sheetal D Ullal1, Ashima G Thomas2, Sahana Devadasa Acharya1
1Department of Pharmacology, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India.
Insights
Long-term use of levetiracetam (LEV) in juvenile rats did not impair learning or memory. However, LEV treatment resulted in a dose-dependent decrease in neuronal density in key brain regions.
Area of Science:
- Neuroscience
- Pharmacology
- Pediatric Neurology
Background:
- Epilepsy affects 2.5 per 1000 children, with levetiracetam (LEV) being a common treatment.
- Short-term studies indicate potential adverse behavioral effects of LEV.
- Limited long-term studies exist on LEV's impact in pediatric populations.
Purpose of the Study:
- To investigate the long-term effects of levetiracetam (LEV) on cognition and behavior in juvenile rats.
- To assess the impact of different LEV dosages on neuronal density in the developing brain.
Main Methods:
- Juvenile Wistar rats received daily oral doses of LEV (200 mg/kg or 400 mg/kg) or a control solution for 21 days.
- Behavioral paradigms were used to evaluate learning and memory.
- Histopathological examination assessed neuronal density in the dentate gyrus, hippocampus, and frontal cortex.
Main Results:
- LEV treatment did not significantly affect learning and memory performance in juvenile rats.
- A significant, dose-dependent decrease in neuronal density was observed in the dentate gyrus, hippocampus, and frontal cortex of LEV-treated rats.
- Histopathological findings indicated potential long-term neurological changes associated with LEV administration.
Conclusions:
- While levetiracetam is effective for epilepsy, long-term use in juveniles warrants caution.
- LEV treatment may lead to a reduction in neuronal count in specific brain areas.
- Vigilant monitoring and careful dosing are recommended for pediatric patients on long-term LEV therapy.
Abstract:
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.
