Abstract
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.
5-HT turnover is reduced in depression. The present results suggest similar impairment of central 5-HT function in normal volunteers treated with fluoxetine. Thus, rather than cause an increase in 5-HT turnover, anti-depressants may correct defects in the 5-HT system. We speculate that anti-depressant treatment which decrease 5-HT turnover may lead to disturbed aggression regulation and violent self-destructive impulses.
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De Sommers, K., van Wyk, M. & Snyman, J.R. Dexfenfluramine-induced prolactin release as an index of central synaptosomal 5-hydroxytryptamine during treatment with fluoxetine. Eur J Clin Pharmacol 46, 441–444 (1994). https://doi.org/10.1007/BF00191908
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DOI: https://doi.org/10.1007/BF00191908