The effects of fenfluramine on blood and tissue serotonin (5-hydroxytryptamine) levels in rats

Abstract

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 mu mol 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.