Antiepileptic drug exposure in the juvenile period does not affect cognitive functions and histomorphology of the hippocampus in adult rats: Antiepileptic drug exposure does not affect cognitive functions in adult rats

Mehmet Azizoğlu; Tevhide Serap Karasalihoğlu; Çetin Hakan Karadağ; Yasemin Karal; Melike Sapmaz Metin

doi:10.28982/josam.8037

Authors

Mehmet Azizoğlu Department of General Pediatrics, Trakya University School of Medicine, Edirne, Turkey https://orcid.org/0000-0002-9982-8005
Tevhide Serap Karasalihoğlu Department of Pediatric Neurology, Trakya University School of Medicine, Edirne, Turkey https://orcid.org/0000-0001-5579-3528
Çetin Hakan Karadağ Department of Pharmacology, Trakya University School of Medicine, Edirne, Turkey https://orcid.org/0000-0002-4763-986X
Yasemin Karal Department of Pediatric Neurology, Trakya University School of Medicine, Edirne, Turkey https://orcid.org/0000-0003-0096-6676
Melike Sapmaz Metin Department of Histology and Embryology, Trakya University School of Medicine, Edirne, Turkey https://orcid.org/0000-0001-9623-4116

DOI:

https://doi.org/10.28982/josam.8037

Keywords:

Antiepileptic drugs, cognitive functions, rats, hippocampus

Abstract

Background/Aim: The impact of long-term antiepileptic drug use during childhood, particularly during critical growth and development phases, remains poorly understood, particularly in terms of its potential side effects on cognitive and locomotor functions in adulthood. This concern is further heightened for patients with a history of multiple drug use.

Methods: In our experimental animal study, 80 rats were divided into eight groups according to gender and the drugs used. Levetiracetam, vigabatrin, and sodium valproate were added to the drinking water from the 4th week to the 12th week postnatally (juvenile period). After the 12th week (adult period), all groups were tested in the following order: the Morris Water Maze, the Contextual Fear Conditioning Test, the Rotarod Performance Test, and a histomorphological investigation of the hippocampus.

Results: The Morris Water Maze Test, which evaluates learning, showed no changes after chronic usage of antiepileptic drugs during the initial 5 days of swimming tests. On the sixth day of memory retention tests, no effect was observed. Additionally, no significant impairment was noted in the Contextual Fear Conditioning Test that assesses associative learning. In the Rotarod test, which evaluates motor coordination, these drugs exhibited no effect on locomotor activity. Furthermore, the histomorphological dissection of the hippocampus revealed no signs of apoptosis or toxicity.

Conclusion: Consequently, the chronic use of levetiracetam, vigabatrin, and sodium valproate did not affect learning, memory, and locomotor activity. Histomorphologically, no neurodegenerative effects on the hippocampus were detected.

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