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 ac id (5-HIAA) concentrations were determined in freely feeding male and female rats 7 days after giving a single dose of D-fenfluramine (3.8 m g/kg, p.o.) or vehicle. Males showed negligible effects except for a s ignificant 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 significan tly lower concentrations of norfenfluramine than the males. Plasma fen fluramine + norfenfluramine concentrations of the females were signifi cantly higher than those of the males. Corresponding brain values show ed smaller but significant differences. Female brain and plasma areas under the curve for fenfluramine + norfenfluramine (0-24 h after admin istration of D-fenfluramine) were 20 and 35% higher than male values. However, results suggest that the sex difference in the effect of D-fe nfluramine on brain 5-HT metabolism is not due to differences in the m etabolism of the drug. (C) 1997 Elsevier Science B.V.