Serotonin but not dopamine is involved in the naloxone-induced luteinizing hormone release in man.

Endogenous opioid peptides exert a tonic inhibition on gonadotropin secretion at the hypothalamic level, but the mechanisms by which they act are still unknown. Previous experimental studies suggest that the endogenous opioid peptides change dopaminergic and serotoninergic tones at the hypothalamic level. We have investigated whether the stimulatory effect of naloxone on luteinizing hormone (LH) secretion is due to its influence on these neurotransmitters. Two experimental models were studied, and two sets of effects on LH secretion induced by intravenous naloxone infusion (20 mg over 2 hours) in 14 normal men 20 to 25 years of age were evaluated: the effect of oral sulpiride (150 mg), a potent dopaminergic antagonist, and the effect of oral fenfluramine (60 mg), a drug that stimulates the serotoninergic receptors by releasing serotonin and inhibiting its reuptake. The study demonstrated that naloxone infusion significantly stimulated the LH secretion throughout the period of observation (P less than 0.01 versus saline). The pretreatment with sulpiride did not change the LH response to naloxone. After fenfluramine pretreatment, naloxone failed to induce any rise in LH secretion. Follicle-stimulating hormone did not show any important variation in either test. The data suggest that in man the stimulatory ability of the opiate receptor antagonist naloxone to elicit a rise in LH plasma levels may involve the serotoninergic, but not the dopaminergic, hypothalamic system. This hypothesis, however, does not exclude the involvement of other hypothalamic neurotransmitters.