Neuroendocrine studies with fluvoxamine: animal data

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.