Absans Epilepsi Modeli Olan Waj/Rij Sıçanlarda Duloksetinin ECoG Aktivitesi Üzerine Etkisi

ÖzAmaç: Birçok epidemiyolojik çalışma epilepsili hastalarda yüksek depresyon ve anksiyete insidansı olduğunu bulmuştur. Duloxetin, serotonin ve norepinefrin geri alımının seçici bir inhibitörüdür (SNRI) ve genellikle majör depresif bozukluğu olan hastalara reçete edilir. Bu çalışmanın amacı, absans-epilepsinin deneysel bir hayvan modeli olan WAG/Rij sıçanlarda epileptiform aktive üzerine duloksetinin etkisini araştırmaktır.Yöntem: WAG/Rij sıçanlar her grupta 7 hayvan bulunan 5 gruba rasgele ayrıldı. Elektrokortikografi (ECoG) değerlendirmesi yapabilmek için kafataslarına tripolar elektrotlar yerleştirildi. Daha sonra, iyileşme periyodunu takiben, her sabah saat 09:00'da üç saat bazal ECoG kayıtları alındı. Sonrasında, duloksetin (1, 5, 10 ve 30 mg/kg) intraperitoneal (i.p) enjekte edildi. Tedavi programı sonrası, ECoG kaydı 3 saat boyunca alındı. Daha sonra tüm hayvanların anksiyete benzeri davranışları davranışsal test olan açık alan testi (AAT) ile test edildi. Diken dalga deşarjlarının (DDD) toplam sayısı ve toplam süresi hesaplandı. Geçilen karelerin sayısı (lokomotor aktivite) ve grooming bölümlerinin süresi AAT'de analiz edildi.Bulgular: Duloksetin (1 mg/kg) dozları ECoG ve AAT parametrelerini değiştirmedi. İntraperitoneal 1 mg/kg duloksetin uygulaması, DDD'lerin sayısı ve süresi açısından istatistiksel olarak anlamlı bir değişiklik göstermedi. 5, 10 ve 30 mg / kg duloksetin dozları kontrol grubuyla karşılaştırıldığı zaman DDD'lerin toplam sayısını ve süresini azalttı, (p <0.05) ve grooming süresini değiştirmeksizin geçilen karelerin sayısını arttırdı. Sonuç: Sunulan çalışmada, duloksetinin, doza bağımlı olarak absans benzeri nöbetleri ve anksiyete benzeri davranışları azalttığı görüldü.

Anahtar Kelimeler:

Duloksetin, Absans Epilepsi, Waj/Rij Sıçan, ECoG, Açık Alan Testi

The effect of duloxetine on ECoG activity of absence-epilepsy model in WAG/Rij rats

Aim: Many epidemiological studies have found a high incidence of depression and anxiety in people with epilepsy. Duloxetine is a selective inhibitor of serotonin and norepinephrine reuptake (SNRI) and commonly prescribed in a patient with major depressive disorder. The aim of this study was to investigate the effect of duloxetine on the WAG/Rij rat in an experimental rat model of absence-epilepsy. Methods: WAG/Rij rats were randomly assigned into 5 groups with 7 animals in each group. Tripolar electrodes were placed on the skull to perform electrocorticography (ECoG) evaluation. Then, following the recovery period, ECoGs were recorded at 09:00 am for 3 hours every day. Subsequently, duloxetine (1, 5, 10 and 30 mg/kg) was injected intraperitoneally (i.p). After the treatment program, ECoG recordings were taken for 3 hours. And then all animal anxiety-like behavior by using the behavioral test, open field test (OFT) was performed after duloxetine (1,5,10 and 30 mg/kg) treatment. The total number and the total duration of the spike-wave discharges (SWDs) were calculated offline. The number of squares crossed (locomotor activity) and the duration of grooming episodes were analyzed in OFT. Results: The doses of duloxetine (1 mg/kg) did not alter ECoG and OFT parameters. The 5, 10 and 30 mg/kg doses of duloxetine decreased the total number and the total duration of SWDs, (p<0.05) and increased the number of squares crossed when compared to with control group (p <0.05) without changing duration of grooming episodes (p> 0.05). Intraperitoneal administering of 1 mg/kg duloxetine did not show any statistically significant change in regard to the number and duration of SWDs. Conclusions: In the present study, duloxetine reduce dose-dependent absences-like seizures and anxiety-like behavior.

Keywords:

Duloxetine, Absence Epilepsy, Waj/Rij Rat, ECoG, Open Field Test,

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