DEXFENFLURAMINE-INDUCED PROLACTIN-RELEASE AS AN INDEX OF CENTRAL SYNAPTOSOMAL 5-HYDROXYTRYPTAMINE DURING TREATMENT WITH FLUOXETINE

Serotonin (5-HT) stimulates prolactin release. In the present study th e ability of dexfenfluramine to increase serum prolactin was used as a n 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 dexfenflurami ne taken with 250 ml water at zero time and no other treatment, or pre treatment with 40 mg fluoxetine at - 8 h, or pretreatment with 20 mg f luoxetine daily for 14 days, or the dexfenfluramine alone 14 days afte r cessation of 14 days of fluoxetine treatment. There were no signific ant differences between the prolactin levels found after dexfenuramine only, dexfenfluramine after a single dose of fluoxetine, and dexfenfl uramine 14 days after cessation of fluoxetine treatment. However, base line levels and those 3 and 4 h after dexfenfluramine administration w ere significantly lower after pretreatment for 14 days with fluoxetine compared to the other three regimens. At 5 h the levels were still lo wer, but not significantly so, as the prolactin level rose approximate ly 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. Furtherm ore, the delayed surge in prolactin release produced by dexfenfluramin e with this regimen suggests 5-HT release from a less accessible pool or accumulation of fluoxetine in the neuronal cytosol and consequent c ompetitive inhibition of 5-HT transport out of the nerve terminal. 5-H T turnover is reduced in depression. The present results suggest simil ar impairment of central 5-HT function in normal volunteers treated wi th fluoxetine. Thus, rather than cause an increase in 5-HT turnover, a nti-depressants may correct defects in the 5-HT system. We speculate t hat anti-depressant treatment which decrease 5-HT turnover may lead to disturbed aggression regulation and violent self-destructive impulses .