Ahmet ATEŞŞAHİN, İzzet KARAHAN, İbrahim PİRİNÇCİ

The effect of fenfluramine on blood and tissue serotonin (5-Hydroxytryptamine) levels in rats

Bu çalışmanın amacı, ratlarda tek ve tekrarlanan dozlarda uygulanan fenfiuramin (FEN)'in beyin, mide ve plazma serotonin (5-Hidroksitriptamin, 5-HT) düzeyleri üzerine olan etkilerinin belirlenmesidir. FEN hayvanlara periton içi yolla tek doz (1,3,10 $mu$ mol/kg) ve ağızdan 21 gün süreyle tekrarlanan dozlar (1,25, 5 ve 10 mg/kg) şeklinde uygulandı. Tek doz uygulamalarını takiben 20, 40, 80 ve 160. dakikalarda; uzun süreli uygulamalarda ise 21 günlük uygulamanın bitmesinden 4 saat sonra dokular alındı. Ayrıca, 1,25 mg/kg dozunda uygulama yapılan gruptaki hayvanlar ilaç uygulaması tamamlandıktan sonraki 2 ve 8.haftalara kadar muhafaza edildi ve dokuları alındı. Doku ve plazma 5-HT düzeyleri yüksek basınçlı sıvı kromatografi (HPLC) cihazında belirlendi. Tek doz fenfiuramin uygulaması yapılan gruplarda beyin 5-HT düzeylerinin kontrol grubuna göre azaldığı, tekrarlanan uygulamalarda ise FEN'in 1,25 mg/kg dozunda beyin 5-HT düzeyleri üzerine pek etkili olmadığı, buna karşılık yüksek dozlarda azalttığı görüldü. Mide 5-HT düzeylerinin hem tek hem de tekrarlanan uygulamalarda arttığı tespit edildi. FEN'in plazma 5-HT düzeylerinde ise belirgin bir şekilde azalmalara neden olduğu görüldü. Sonuç olarak FEN'in beyin ve plazma 5-HT düzeylerinde azalmaya; mide de ise artışlara neden olduğu belirlendi.

Ratlarda fenfluraminin kan ve doku serotonin (5-hidroksitriptamin) düzeyleri üzerine etkileri

The aim of this study was to investigate the effect of fenfluramine (FEN) administered at single and repeated doses on brain, stomach and plasma Serotonin (5-Hydroxytryptamine, 5-HT) levels in rats. FEN was injected intraperitoneally at single doses (1, 3 and 10 μmol $kg^{-1}$ ) and given orally at repeated doses (1.25, 5 and 10 mg $kg^{-1}$ ) for 21 days. The tissues and plasma samples were collected 20, 40, 80 and 160 minutes after the single dose administrations and 4 h after the last dose administration in repeated experiments. In addition, the rats treated with the dose of 1.25 mg kg"1 were maintained until 2 and 8 weeks and the tissues were taken at these times. The 5-HT levels in the tissue and plasma were measured by using high performance liquid chromatography (HPLC). The levels of brain 5-HT were decreased at the single FEN doses when compared with the control group. At the repeated experiments, although no effect was observed at the dose of 1.25 mg $kg^{-1}$ ; decreases were determined in brain 5-HT levels at the high doses. The levels of 5-HT in the stomach were found to increase in both single and repeated administrations. Decreases in levels of plasma 5-HT were determined in all experimental groups. In conclusion, while fenfluramine was determined to decrease brain and plasma 5-HT levels generally, it increased the levels of stomach 5-HT.

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