Peripheral hormonal responses to D-fenfluramine as a probe of central serotonergic function in humans

We tested the hypothesis that D-fenfluramine (DFEN)-elicited cortisol (CORT ) release in humans may be mediated by a direct effect on the adrenal gland by pretreating subjects with dexamethasone (DEX), to prevent release of AC TH from the pituitary, followed by a DFEN challenge test. Eight healthy sub jects (four males: four female) (mean age = 38.1 +/- 8.4 years (SD)] were s tudied > 1 week apart (same phase of menstrual cycle) and testing order was randomised. On the with-DEX day (DEX+), subjects took 2 mg DEX orally at 1 0 p.m.; 30 mg DFEN was then given orally at 9 a.m. and samples were taken a t 0-5 h for PRL and CORT. Peak hormone responses (Delta values) were calcul ated by subtracting baseline values from the maximum levels post-DFEN admin istration. Peak and baseline hormonal values were compared between the two test conditions: DFEN-induced CORT and PRL responses were compared across a ll time points, with and without DEX. There was no significant difference i n Delta PRL between the two test conditions (DEX- and DEX+), but Delta CORT values were significantly reduced after DEX: mean Delta CORT DEX- = 68.4 /- 26.3 nmol/l, DEX+ = 0.0 nmol/l (all blunted) (df 7.1; P = 0.03). The com pletely blunted peripheral cortisol response indicates that DFEN cortisol r esponses are of central origin only.