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We studied the effect of 3 weeks treatment with the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, on hormonal and psychological responses to buspirone, a 5-HT1A receptor partial agonist which also binds to dopamine receptors, in normal male volunteers. Eleven subjects received buspirone, 30 mg, and placebo before, and in week 3 of fluvoxamine treatment (mean dose 127 mg/day). Placebo and buspirone were given in a balanced order, double-blind. Buspirone significantly elevated plasma prolactin (PRL) and growth hormone (GH) concentrations but had no significant effect on cortisol (CORT) or temperature. Significant psychological effects of lightheadedness, tiredness and difficulty thinking occurred. Fluvoxamine treatment resulted in a nearly 3-fold increase in plasma buspirone with a similar enhancement of the PRL response. In contrast the GH and psychological responses were blunted. The increased buspirone concentrations are likely to be due to inhibition of first pass liver metabolism by fluvoxamine acting on the cytochrome P-450 system. The PRL response is probably mediated by antagonism of pituitary dopamine-D2 receptors and its enhancement by fluvoxamine treatment may be a pharmacokinetic effect. The blunting of GH and psychological responses suggest that 5-HT1A receptor function is reduced by chronic fluvoxamine treatment.

The prolactin response to intravenous clomipramine, a 5-HT uptake inhibitor, was significantly attenuated in 12 patients with major depression. In contrast, in a further 12 depressed patients, the PRL responses to thyrotropin-releasing hormone, which acts directly on the pituitary to release PRL, were not reduced. These findings suggest that the reduction in 5-HT-mediated PRL release seen in depressed patients is due to an impairment of brain 5-HT function rather than a pituitary abnormality.

Pretreatment of nine healthy subjects with the non-selective 5-HT receptor antagonist, metergoline (4 mg), abolished the increase in plasma prolactin produced by the anxiolytic drug, buspirone (15 mg). While these findings are consistent with a role for 5-HT receptors in the stimulatory effect of buspirone on plasma prolactin, a dopaminergic mechanism cannot be excluded by the present data.

The effects of the 5-hydroxytryptamine (5-HT) uptake inhibitor clomipramine on the prolactin (PRL) and growth hormone (GH) responses to L-tryptophan (LTP) were assessed in six normal subjects. Oral administration of 20 mg clomipramine 2 h prior to LTP infusion (50 mg/kg) significantly enhanced both endocrine responses, suggesting that the increases in plasma PRL and GH produced by LTP are mediated by 5-HT pathways. These findings, taken together with previous observations that 5-HT2 receptor antagonists do not attenuate the PRL response to LTP, suggest that the 5-HT-induced release of PRL in man may be mediated by 5-HT1 receptors.

Sleep-related prolactin secretion and prolactin responses to the infusion of low doses of the dopamine antagonist, metoclopramide, and thyrotropin-releasing hormone were measured in 11 female volunteers before and after undertaking a diet in which they lost a mean of 3.1 kg in weight in 3 weeks. No effect of weight loss on these measures was found, but there was a significant, although modest, reduction in fasting plasma tryptophan concentration without any change in the concentration of competing amino acids.

Acute dietary tyrosine depletion has previously been shown to reduce dopamine neurotransmission in both animals and humans. In this study, we investigated the effects of brain dopamine depletion, through acute tyrosine and phenylalanine depletion, on plasma prolactin, mood and neuropsychological function in 12 normal subjects. In a randomized, double-blind, cross-over design, subjects received two amino-acid drinks separated by a week, a nutritionally balanced mixture (Bal) and on the other occasion a tyrosine and phenylalanine deficient mixture (TP-). The plasma ratio of tyrosine and phenylalanine to the other large neutral amino acids decreased significantly on the TP- occasion (-78.7%, p < 0.0001) and there was an increase in plasma prolactin concentration relative to the balanced drink in the seven subjects for whom results were available for both occasions (p < 0.02). Acute tyrosine depletion did not alter mood as measured by visual analogue scale ratings, and measures of memory, attention and behavioural inhibition were also unaffected. Our results are consistent with acute dietary tyrosine depletion causing a reduction in brain dopamine neurotransmission but raise questions about how robust or consistent the effects are on psychological function. [ABSTRACT FROM AUTHOR]

The effects of the selective 5-HT2 receptor antagonist, ritanserin, on the growth hormone (OH) and prolactin (PRL) responses to intravenous L-tryptophan (LTP) were assessed in 8 normal volunteers. Administration of ritanserin (40 mg orally) prior to infusion of LTP (5 g) significantly enhanced the PRL responses but not those of GH. The results are consistent with previous proposals that the endocrine responses to LTP are mediated by 54-HT1 rather than 5-HT2 receptors and also suggest that 5-HT2 receptor antagonists may increase certain 5-HT1 mediated responses in the human brain. [ABSTRACT FROM AUTHOR]