Neuroendocrine studies with fluvoxamine: animal data.

1 Administration of the potent 5-hydroxytryptamine (5-HT) re-uptake inhibitor fluvoxamine (25 mg/kg i.p. for 14 days) to adult cycling female rats did not alter either the number of oestrous episodes or the plasma concentrations of luteinizing hormone determined on days 2, 9 and 14 of treatment. 2 Fluvoxamine (25 mg/kg i.p.) induced in male rats a clear-cut lowering of beta-endorphin-like immunoreactivity from the anterior pituitary, but not the neurointermediate lobe, and increased concomitantly plasma levels of beta-endorphin and beta-lipotropin. 3 Fluvoxamine (12.5 and 25 mg/kg i.p.) stimulated, although not strikingly, prolactin (PRL) secretion in adult male rats, and at 25 mg/kg i.p. potentiated the PRL-releasing effect of 5-hydroxytryptophan (30 mg/kg i.p.). 4 In male rats treated daily with fluvoxamine (25 mg/kg i.p.) the PRL-releasing effect of an additional acute fluvoxamine administration (same dose) was abolished after 4 days maintenance treatment. One week after withdrawal of maintenance, which had been given for 14 days, the challenge dose of fluvoxamine was still unable to raise plasma PRL levels. 5 The endocrine effects of acute fluvoxamine administration are compatible with activation of 5-HT neurotransmission in the central nervous system. The mechanism(s) underlying tolerance to the PRL-releasing action of the drug is presently obscure. Its elucidation should provide insight into the mechanism of action of antidepressant drugs affecting 5-HT function.