Differential Effects of Valproic Acid and Levetiracetam on Freezing Behavior in A Pentylenetetrazol-Induced Seizure Model in Rats

Öz

Aim Epileptic seizures are often accompanied by cognitive and behavioral alterations. Valproic acid (VPA) and levetiracetam (LEV) are widely used antiepileptics with different neurobehavioral profiles. This study aimed to investigate whether clopidogrel (CLP), an antiplatelet agent commonly co‑administered in cerebrovascular diseases, influences the anticonvulsant efficacy of VPA and LEV in a pentylenetetrazol (PTZ) ‑ induced rat seizure model. Material and Method Forty-two adult male Wistar rats were randomly assigned into seven groups (n=6): Control, PTZ, CLP, VPA, LEV, VPA+CLP, and LEV+CLP.  PTZ (60 mg/kg i.p.) was used to induce seizures. Freezing behavior was evaluated at baseline, 24h and 48 h via the passive avoidance test. Statistical analysis was performed with repeated-measures ANOVA and Tukey’s post-hoc test. Results Freezing time differed significantly among experimental groups (p<0.05). VPA and VPA+CLP groups demonstrated significantly reduced freezing times at all time points compared with other groups (p < 0.05). LEV and LEV+CLP groups showed freezing responses comparable to the control group (p>0.05). CLP alone did not significantly affect freezing behavior. Conclusion  Clopidogrel does not affect the anticonvulsant or behavioral profiling of either valproic acid or levetiracetam in a PTZ‑induced seizure model. While VPA impairs fear‑related memory, LEV preserves cognitive performance

Anahtar Kelimeler

• Epilepsy
• valproic acid
• levetiracetam
• clopidogrel
• PTZ
• freezing behavior

Pentylenetetrazol ile İndüklenen Nöbet Modelinde Valproik Asit ve Levetirasetamın Donakalım Davranışı Üzerine Farklı Etkileri

Öz

Epileptik nöbetlere sıklıkla bilişsel ve davranışsal değişiklikler eşlik etmektedir. Valproik asit (VPA) ve levetirasetam (LEV), farklı nörodavranışsal profillere sahip, yaygın olarak kullanılan antiepileptik ilaçlardır. Bu çalışmanın amacı, serebrovasküler hastalıklarda sıklıkla birlikte kullanılan bir antiplatelet ajan olan klopidogrelin (CLP), pentilentetrazol (PTZ) ile oluşturulan sıçan nöbet modelinde VPA ve LEV’nin antikonvülzan etkinliği üzerindeki etkisini araştırmaktır. Gereç ve Yöntem Kırk iki erişkin erkek Wistar sıçan rastgele olarak yedi gruba ayrıldı (n=6): Kontrol, PTZ, CLP, VPA, LEV, VPA+CLP ve LEV+CLP. Nöbet oluşturmak amacıyla PTZ (60 mg/kg, i.p.) uygulandı. Donakalım (freezing) davranışı, pasif kaçınma testi ile başlangıçta, 24. saatte ve 48. saatte değerlendirildi. İstatistiksel analiz, tekrarlı ölçümler için varyans analizi (ANOVA) ve Tukey post-hoc testi kullanılarak gerçekleştirildi. Bulgular Donakalım süresi deney grupları arasında anlamlı farklılık gösterdi (p<0,05). VPA ve VPA+CLP gruplarında, tüm zaman noktalarında diğer gruplara kıyasla anlamlı derecede daha düşük donakalım süreleri saptandı (p<0,05). LEV ve LEV+CLP gruplarında ise donakalım yanıtlarının kontrol grubuna benzer olduğu görüldü (p>0,05). CLP’nin tek başına uygulanması, donakalım davranışı üzerinde anlamlı bir etki oluşturmadı. Sonuç Klopidogrel, PTZ ile oluşturulan nöbet modelinde ne valproik asidin ne de levetirasetamın antikonvülzan etkinliğini veya davranışsal profilini etkilemektedir. VPA korkuya bağlı belleği olumsuz etkilerken, LEV bilişsel performansı korumaktadır.

Anahtar Kelimeler

• Epilepsi
• valproik asit
• levetirasetam
• klopidogrel
• PTZ
• donakalım davranışı

Kaynakça

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