Naloxone does not modify fenfluramine-induced prolactin increase in obese patients.
OBJECTIVE
To evaluate whether the supposed physiological interaction between serotoninergic and opioidergic pathways in the modulation of PRL release is preserved in human obesity, a pathological condition in which these two systems are greatly impaired.


METHODS
According to a single-blind randomized procedure, three tests were performed: test A (oral placebo + saline infusion over 5 hours), test B (fenfluramine, a well known serotoninergic drug, 60 mg orally + saline infusion over 5 hours) and test C (fenfluramine at the same dose + naloxone, an opiate receptor antagonist, infusion over 5 hours at a dose of 3 mg/h).


METHODS
Ten obese women (body mass index 34.4 +/- 2.3 kg/m2, mean +/- SE) and ten normal-weight sex and age-matched subjects (body mass index 22.3 +/- 2.4 kg/m2) volunteered for the study.


METHODS
At each test, blood samples for PRL determination were collected in basal conditions (time 0) and every hour for 5 hours. Plasma PRL was determined by radioimmunoassay.


RESULTS
In controls, naloxone significantly reduced the clear-cut PRL increase induced by fenfluramine. In obese patients, serotoninergic stimulation caused an increment in PRL levels similar to that in the controls, but opioid receptor blockade by naloxone did not affect this response.


CONCLUSIONS
These findings confirm that there is a physiological relationship between the serotoninergic and the opioidergic systems in the control of PRL secretion and show that this interaction is not present in obese subjects. Our data provide indirect proof of the functional impairment of these two systems in human obesity.
Argenio
G F
GF
Fisiopatologia Endocrina, Clinica Medica 1a, University of Pisa, Italy.
Bernini
G P
GP
Vivaldi
M S
MS
del Corso
C
C
Santoni
R
R
Franchi
F
F
D000293:Adolescent; D000328:Adult; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology*; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D016037:Single-Blind Method
D005277:Fenfluramine; D009270:Naloxone; D011388:Prolactin