# Cognitive and Behavioral Effects of Levetiracetam in Juvenile Rats

**Authors:** Sheetal D. Ullal, Ashima G. Thomas, Sahana Devadasa Acharya, Vandana Blossom, Rajeshwari Shastry

PMC · DOI: 10.1002/prp2.70226 · Pharmacology Research & Perspectives · 2026-03-05

## TL;DR

This study examines the long-term effects of the epilepsy drug levetiracetam on cognition and brain structure in juvenile rats.

## Contribution

The study provides new insights into the long-term behavioral and histopathological effects of levetiracetam in juvenile rats.

## Key findings

- LEV treatment did not impair learning and memory in juvenile rats.
- LEV caused a dose-dependent decrease in neuronal density in key brain regions.

## 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.

## Linked entities

- **Chemicals:** Levetiracetam (PubChem CID 5284583), LEV (PubChem CID 9823820)
- **Diseases:** Epilepsy (MONDO:0005027)

## Full-text entities

- **Genes:** Ca2 (carbonic anhydrase 2) [NCBI Gene 54231] {aka Car2}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, SV2A (synaptic vesicle glycoprotein 2A) [NCBI Gene 9900] {aka DEE113, SLC22B1, SV2}, Ca3 (carbonic anhydrase 3) [NCBI Gene 54232] {aka Car3}, Sv2a (synaptic vesicle glycoprotein 2a) [NCBI Gene 117559] {aka Sv2}, Ca4 (carbonic anhydrase 4) [NCBI Gene 29242] {aka Car4}
- **Diseases:** cognitive impairment (MESH:D003072), memory impairment (MESH:D008569), neuronal damage (MESH:D009410), depressant (MESH:D003866), agitation (MESH:D011595), neuropsychiatric (MESH:C000631768), somnolence (MESH:D006970), Epilepsy (MESH:D004827), seizure (MESH:D012640), neurologic disorder (MESH:D009461), hyperthermia (MESH:D005334), TRC (MESH:C535679), mood disorders (MESH:D019964), learned helplessness (MESH:D007859), neurotoxic (MESH:D020258), behavioral disturbances (MESH:D001523), Alzheimer's disease (MESH:D000544), behavioral deficits (MESH:D019958), neurological condition (MESH:D019636), shock (MESH:D012769)
- **Chemicals:** formalin (MESH:D005557), LEV (MESH:D000077287), Gum acacia (MESH:D006170), Chemicals (-), acetic acid (MESH:D019342), cresyl violet (MESH:C028911), water (MESH:D014867), Paraffin (MESH:D010232), NaCl (MESH:D012965)
- **Species:** Gallus gallus (bantam, species) [taxon 9031], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** H600L, C +- 3 C

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12962872/full.md

## References

19 references — full list in the complete paper: https://tomesphere.com/paper/PMC12962872/full.md

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Source: https://tomesphere.com/paper/PMC12962872