The effect of D-fenfluramine on brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in male and female rats.

Brain regional 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in freely feeding male and female rats 7 days after giving a single dose of D-fenfluramine (3.8 mg/kg, p.o.) or vehicle. Males showed negligible effects except for a significant decrease of 5-HT in the rest of the cortex, whereas females showed significant decreases of 5-HT and 5-HIAA in the frontal cortex, the rest of the cortex, hippocampus and hypothalamus; 5-HT was also decreased in female midbrain. Females had substantially higher plasma and brain concentrations of fenfluramine and moderately but significantly lower concentrations of norfenfluramine than the males. Plasma fenfluramine + norfenfluramine concentrations of the females were significantly higher than those of the males. Corresponding brain values showed smaller but significant differences. Female brain and plasma areas under the curve for fenfluramine + norfenfluramine (0-24 h after administration of D-fenfluramine) were 20 and 35% higher than male values. However, results suggest that the sex difference in the effect of D-fenfluramine on brain 5-HT metabolism is not due to differences in the metabolism of the drug.