A link between oxytocin and serotonin in humans: supporting evidence from peripheral markers

Pharmacological studies indicate a functional interaction between the serotonergic and oxytocinergic systems. In particular, some selective serotonin (5-HT) reuptake inhibitors, such as citalopram and fluvoxamine, seem to exert part of their antidepressant effects through oxytocin (OT) release. Further, the administration of fenfluramine, a serotonergic agonist, to healthy subjects increases plasma OT levels. Interestingly, immunocytochemical and double-immunofluorescent techniques revealed a high degree of overlap between 5-HT transporter (SERT)-labeled fibers and OT-containing cells in the paraventricular and supraoptic nuclei of primate hypothalamus. These findings suggest that the influence of 5-HT on OT system might be mediated by SERT. In this study, we explored the possible existence of a link between OT and SERT in human subjects, by means of two peripheral markers, the platelet SERT, as measured by [³H]-paroxetine ([³H]-Par) binding, and plasma OT levels. As far as [³H]-Par binding parameters are concerned, the Bmax (mean ± SD, fmol/mg protein) was 1155 + 130 and the Kd (mean ± SD, nM) was 1.31 ± 0.61. The OT plasma levels (mean ± SD, pg/ml) were 1.14 ± 1.07. A significant and positive correlation was found between plasma OT levels and Kd values (correlation coefficient: r: 0.466, p = .038). This result represents the first evidence of an interaction between OT and SERT, as measured by [³H]-Par binding, at peripheral levels in humans. Given the several activities mediated by both OT and 5-HT, such a relationship might provide new perspectives and insights into psychiatric disorders and/or social relationship disturbances, as well as novel treatment strategies overcoming and/or integrating the serotonergic paradigm.