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Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pretreatment of volunteers with fluoxetine. Following a single-blind, random design, on each experimental day each volunteer received 60 mg dexfenfluramine taken with 250 ml water at zero time and no other treatment, or pretreatment with 40 mg fluoxetine at -8 h, or pretreatment with 20 mg fluoxetine daily for 14 days, or the dexfenfluramine alone 14 days after cessation of 14 days of fluoxetine treatment. There were no significant differences between the prolactin levels found after dexfenfluramine only, dexfenfluramine after a single dose of fluoxetine, and dexfenfluramine 14 days after cessation of fluoxetine treatment. However, baseline levels and those 3 and 4 h after dexfenfluramine administration were significantly lower after pretreatment for 14 days with fluoxetine compared to the other three regimens. At 5 h the levels were still lower, but not significantly so, as the prolactin level rose approximately 110% compared to the baseline and 4 h values. The reduction in the median basal serum prolactin level by almost two-thirds after 14 days of fluoxetine treatment suggests a decrease in 5-HT turnover. Furthermore, the delayed surge in prolactin release produced by dexfenfluramine with this regimen suggests 5-HT release from a less accessible pool or accumulation of fluoxetine in the neuronal cytosol and consequent competitive inhibition of 5-HT transport out of the nerve terminal.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: The present placebo-controlled study was designed to compare the effect of acute pretreatment with dexfenfluramine and fluoxetine on the plasma aldosterone response to metoclopramide. Study Participants and Design: Ten healthy ambulatory male volunteers participated. Following a single-blind, randomised design, each volunteer received metoclopramide as an intravenous bolus of 10mg at 0700 hours on each experimental day. Participants were pretreated at 2200 hours the previous evening and 0500 hours in the morning with one of the following: fluoxetine 20mg, dexfenfluramine 30mg, or placebo. Results: In response to metoclopramide administration, the maximum concentration was significantly higher (p = 0.004) than baseline with placebo, fluoxetine and dexfenfluramine. The area under the curve of dexfenfluramine was significantly larger than that with both placebo (p = 0.007) and fluoxetine (p = 0.004), while that of fluoxetine was significantly larger than that of placebo (p = 0.01). Conclusion: Acute pretreatment with both dexfenfluramine and fluoxetine caused an enhancement of metoclopramide-induced aldosterone secretion, probably by augmenting serotonergic neurotransmission via serotonin (5-HT) receptors. The plasma aldosterone levels were significantly higher with dexfenfluramine compared with fluoxetine, probably as a result of larger 5-HT concentrations being available for stimulation of glomerulosa cell activity. [ABSTRACT FROM AUTHOR]